COVID-19 Vaccine in Pregnant and Lactating Women: A Review of Existing Evidence and Practice Guidelines
Round 1
Reviewer 1 Report
Garg et al. review article describes the vaccination of pregnant and breastfeeding persons against COVID-19, a rather susceptible group with little clinical trials.
- Major points:
- The authors' chose a general title to the topic "COVID-19 Vaccine in Pregnant and Lactating Women: A review of existing evidence and practice guidelines". However the authors only address the FDA approved vaccines with little mention of WHO guidelines.
Line 68 mentions six vaccines only that are used in the USA and FDA approved while WHO has included more vaccines and are used widely worldwide including sinopharm and sinovac.
The WHO Emergency Use Listing (EUL) includes: Pfizer/BioNtech Comirnaty vaccine, SII/Covishield and AstraZeneca/AZD1222 vaccines, Janssen/Ad26.COV 2.S, Moderna COVID-19 vaccine (mRNA 1273), Sinopharm COVID-19 vaccine and Sinovac-CoronaVac.
All these vaccines must be addressed in the review article.
2. Table 1 needs much improvement as instructed in the attached PDF.
3. Rewrite lines 295 to 297 as not clear at all.
4. lines 305-310 about the transfer of COVID-19 antibodies from the mother to child transplacental or via breastfeeding contradicts to the previously mentioned data line 287.
5. The special considerations needs to be rewritten in form of a paragraph.
- Minor points:
- Line 93, which population is the author mentioning.
- line 42, females not female - also revise the abstract and introduction grammar.
- lines 245 to 251 needs formatting.
- line 291 is "showed" not "should"
- More typos and grammar errors are highlighted in the PDF attached.
Comments for author File: 
Comments.pdf
Author Response
We thank the reviewer for their comments and have addressed all the comments below. All changes to the manuscript have been marked in red.
- The authors' chose a general title to the topic "COVID-19 Vaccine in Pregnant and Lactating Women: A review of existing evidence and practice guidelines". However the authors only address the FDA approved vaccines with little mention of WHO guidelines. Line 68 mentions six vaccines only that are used in the USA and FDA approved while WHO has included more vaccines and are used widely worldwide including sinopharm and sinovac.
The WHO Emergency Use Listing (EUL) includes: Pfizer/BioNtech vaccine, SII/Covishield and AstraZeneca/AZD1222 vaccines, Janssen/Ad26.COV 2.S, Moderna COVID-19 vaccine (mRNA 1273), Sinopharm COVID-19 vaccine and Sinovac-CoronaVac.
All these vaccines must be addressed in the review article.
Response: We accept the reviewers recommendation and have added the information on these vaccines in our article as well as in the table 1.
- Table 1 needs much improvement as instructed in the attached PDF.
Response: Table 1 has been edited to include data for the additional vaccines and to enhance clarity by merging cells when possible to reduce redundancy.
- Rewrite lines 295 to 297 as not clear at all.
Response: We have edited the aforementioned lines to enhance clarity. It now reads ") Shimabukuro et al. reported pregnancy loss occurred in 13.9% of participants that had a completed pregnancy (i.e., live-born infant, spontaneous abortion, induced abortion, or stillbirth). They also note adverse neonatal outcomes of preterm birth (9.4%), and small size for gestational age (3.2%). No neonatal deaths were reported."
- lines 305-310 about the transfer of COVID-19 antibodies from the mother to child transplacental or via breastfeeding contradicts to the previously mentioned data line 287.
Response: The line 305-310 is regarding the transfer of antibodies via breast milk whereas the line 287 is regarding transplacental transfer of vaccine particles.
- The special considerations needs to be rewritten in form of a paragraph.
Response: We accept the suggestion and have rewritten the section in the form of a paragraph.
- Minor points:
- Line 93, which population is the author mentioning.
Response: These numbers are from the phase 3 clinical trials of respective vaccines. We have edited the lines to specify as such.
- line 42, females not female - also revise the abstract and introduction grammar.
Response: We have addressed it and made the changes.
- lines 245 to 251 needs formatting.
Response: The lines have been reformatted to remove the accidental paragraph break introduced at formating.
“They only reported unsolicited data on adverse events related to pregnancy including miscarriage. In Pfizer/BioNTech (1/12; 8%) and Moderna vaccine trials (1/7; 14%), miscarriage was reported only in placebo group. In Janssen vaccine trial, reported adverse events during pregnancy included spontaneous abortion (1 in vaccine group, 0 in placebo group), incomplete abortion (0 in vaccine group, 1 in placebo group), elective abortion (0 in vaccine group, 2 in placebo group) and ectopic pregnancy (1 in vaccine group, 0 in placebo group). The results are summarized in table 2”
- line 291 is "showed" not "should"
Response: We have made the change.
- More typos and grammar errors are highlighted in the PDF attached.
Response: We have addressed the highlighted sections with relevant changes.
Reviewer 2 Report
In this review, the authors attempt to address one of the glaring issues in the COVID19 vaccination program- the pregnant and lactating women. Often time this group is excluded in clinical trials testing a new vaccine for the first time (out of an abundance of caution) and COVID-19 is no exception. However, given the severity of the infection, it is essential to investigate if the vaccines pose a severe safety threat to pregnant/lactating women. The authors have done a great job looking into existent data of reported pregnancies (accidental -while being enrolled in the trial) and retrospective survey reports submitted by pregnant women after being vaccinated in the US and UK.
I only have minor comments. Please see below.
-Since this review focuses on pregnant women, the introductory part with the vaccine overview in the table is informative but not necessarily pertinent to the topic.
Instead, a table with enrolled pregnant women under various vaccination programs and their reported adverse events (or rather the lack of) would be beneficial for the readers. The ‘special consideration’ section at the end of the review will make a nice addition to the table too.
-The clinical trial announced by different pharmas that are about enrolled pregnant women for COVID19 vaccinations should also be presented in a tabular format.
Modera has announced a
-Moderna
Data collected so far include over 50,000 pregnant women and show no serious vaccine-related adverse events
-It would probably help the review if the authors could expand a bit more on what they imply by 1)adverse events and 2) serious adverse events. In general, it would help the authors to discuss what side effects those pregnant women reported.
-Perhaps it would be interesting to draw comparisons with formerly approved vaccines (mRNA/ viral vectors) that can be administered safely to pregnant women summarized in the publication below
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992376/
-Some drawbacks of this review should be discussed.
Author Response
Since this review focuses on pregnant women, the introductory part with the vaccine overview in the table is informative but not necessarily pertinent to the topic. Instead, a table with enrolled pregnant women under various vaccination programs and their reported adverse events (or rather the lack of) would be beneficial for the readers. The ‘special consideration’ section at the end of the review will make a nice addition to the table too.
Response: We have included the information about pregnant women accidentally enrolled in vaccine trials in Table 2 and included the data presented in special considerations in Table 1.
-The clinical trial announced by different pharmas that are about enrolled pregnant women for COVID19 vaccinations should also be presented in a tabular format. Modera has announced a
-Moderna Data collected so far include over 50,000 pregnant women and show no serious vaccine-related adverse events
Response- Thank you for the suggestion. However, the results from those vaccine trials have not yet been made available. The data reported in v-safe surveillance system has already been mentioned in the manuscript text.
-It would probably help the review if the authors could expand a bit more on what they imply by 1)adverse events and 2) serious adverse events. In general, it would help the authors to discuss what side effects those pregnant women reported.
Response- Thank you for the suggestion. We have added the definition used by the referenced author for clarity.
-Perhaps it would be interesting to draw comparisons with formerly approved vaccines (mRNA/ viral vectors) that can be administered safely to pregnant women summarized in the publication below
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992376/
Response : We thank the reviewer for the suggestion and for the included article. However, we feel that a detailed comparison between covid-19 vaccines and previously used mRNA and viral vector vaccines would be beyond the scope of this article.
-Some drawbacks of this review should be discussed.
Response: We have added a section on the limitations of the review.
