PONE-D-21-18898Antenatal depression: Associations with birth and neonatal outcomes among women attending maternity care in Harare, ZimbabwePLOS ONE

Dear Dr. Kaiyo-Utete,

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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Additional Editor Comments:

Both reviewers see important merit in the submitted manuscript, but they both raise important methodological and data analysis inquiries that need to be addressed.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: No

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This is a very interesting paper aiming to examine the prevalence of antenatal depression and its associations with birth and neonatal outcomes in Zimbabwe. The manuscript is clear, well written and discusses about an important topic. However, there are several pieces of information missing and several points that require improvement, as described below:

Abstract:

Please make it already very clear in the abstract what are the main aims of the study.

Introduction

Throughout the text, there are some typos and grammar mistakes. Please proofread and review the paper carefully.

The introduction is very well-written, but I am missing a more thorough review of the studies conducted in Africa, but specifically in Zimbabwe.

Also, some citations are missing (e.g. “Its under treatment has been associated with negative effects

on the mother and her developing foetus.“;“ paucity of evidence on the associations of antenatal depression in the Zimbabwean context, which has a high prevalence of antenatal depression“). The reader has no clue if certain statements refer to the African or to the global context or if they are based on assumptions or evidence. Please cite accordingly.

Methods

Was the validation of the PHQ-9 and EPDS done with this same population or just in the same health centres?

Please describe in details how the randomization process for the maternity clinics was conducted.

Did the participants provide written consent? If yes, please clearly state it.

Please describe in details the power analysis conducted to decide on the number of participants needed.

The prenatal depression diagnostics was done with the SCID interview. How did you account for physical symptoms relevant to the depression diagnosis which are normal in pregnancy?

What is the relevance of the variable “initiated breastfeed within 1h post-delivery” for the research question? How is this associated with prenatal depression given that many times, depending on the maternity care centre procedures, this initiation or lack of, is not a maternal choice?

Did the authors account for current pregnancy complications or only for past complications? If not current, why not?

Please cite the studies supporting the choice for the confounding variables. I am unsure if they belong to the global or regional level.

Authors mentioned that participants were recorded as depressed or non-depressed. But from those scored as depressed, what is the percentage/proportion of minor and major depression? Please add this to the text.

Authors mentioned that the depressed participants were referred to the mental health nurse or psychotherapy. When did participants started with this treatment? What kind of treatment was given? How has this impacted mental health measurements postpartum? You need to adjust for this important variable in the analysis.

Results

Were there any differences between the participants who remained until the end of the study and the N=21 who were lost in the follow up?

Participants can be either primipara or multiparas, not both. Please correct it in the text.

Table1: the authors mentioned that covariates were chosen based on previous literature and evidence, but aren’t religion and social support quite important in the regional context? Also, were the randomly selected clinics settled in a rural or urban region? This should be acknowledged, given that if they are in an urban setting, women attending it might not be comparable to those in a rural setting with less resources to attend and pay for the maternity care.

Please state the percentage of participants diagnosed with minor and major depression in the sample in Table 1.

Although the authors clearly described depression levels and infant characteristics in the postpartum phase, it would be interesting to see a table with the outcomes from babies whose mothers were antenatally depressed. It is unclear, especially considering prenatally depressed mothers were offered and potentially received treatment during pregnancy, how many of those were still depressed in the postpartum and the potential effects/improvement on baby outcomes for those receiving therapy.

Table 2: It would be important to add the percentage of babies not being breastfed at all (e.g. only formula feeding).

Discussion

In the second paragraph, authors justify the association between antenatal depression and LBW risk behaviours. However, it is important to contextualize it to your sample. Based on Table 1, the participants have a low percentage of risk behaviours. Maybe you could justify it if the depressed moms have a higher rate of risky behaviours upon comparison with the non-depressed one. But this needs to be described in text or tables.

Authors also mentioned cultural barriers associated with breastfeeding. What are those in Zimbabwe? It would be important to contextualize it in the region where the study was conducted as well as with the sample here studied.

Please make sure to make it clear that the association between prenatal depression and exclusive breast was quite small and how relevant is it.

Did the authors considered that the lack of statistical significance between depression and certain outcomes may be due to the fact that most participants were diagnosed with minor depression? Since this is not clearly described in text, the reader has no clue if this is a possibility. Please make it clear.

Reviewer #2: In this original article, the Authors aim to determine the association between antenatal depression during the second or third trimester and birth and neonatal outcomes assessed at 6 weeks post-partum in a cohort of 354 Zimbabwean women. They found that a diagnosis of major and minor antenatal depression was associated with low birth weight in the new-borns, with a lower rate of exclusive breastfeeding and with higher rate of depressive symptoms beyond the EPDS cut-off.

The study is interesting because to date only few prospective studies evaluated the impact of prenatal depression in sub-Saharian countries. Some methodological issues, hovewer, lower my enthusiasm for the manuscript. Specifically the authors considered the antenatal depression as the main predictor of ten different outcomes. In a second step of the analyses they controlled for eight different covariates. Moreover they dichotomised most of the variable with the risk of losing some important information.

If possible I’d like the authors to address the following queries:

Introduction

• The authors should consider adding a reference to the sentence “Its undertreatment has been associated with negative effects on the mother and her developing foetus” (see Mitchell & Goodman, Arch Womens Ment Health, 2018)

• When referring to the studies that failed in identifying an association between depressive symptoms and neonatal outcomes the authors might consider to discuss the role of symptoms severity, comorbid anxiety and medications (see Ossola et al., J Matern Fetal Neonatal Med, 2021). This seems particularly relevant as it is not clear whether (or in which percentage) the sample was treated.

• When stating the aims the authors conclude that “if antenatal depression is associated with poor birth and neonatal outcomes, it would emphasize the importance of screening for it as part of routine prenatal care”. This however is only partly descriptive of the study design as the authors also consider post-partum depressive symptoms as a possible maternal outcome. This should be clarified early on.

Methods and Results

• I’m not sure I fully understand the meaning of “a medical doctor attending to severe chronic conditions monthly”. Do the authors mean that an obstetrician-gynaecologists was available only once a month for the most severe patients? Was the psychiatrist that administered the SCID-IV similarly available?

• The authors detailed the power analysis as follow “Assuming a 39% prevalence of antenatal depression, we calculated that a sample of 366 women was needed to achieve a 5% precision at 95% confidence intervals”. I’m not sure I understand based on which aim this sample size was calculated.

• When defining the data collection procedures would be helpful to detail which information were collected at baseline (see Table 1) and how these were dichotomised. As noted above the authors should justify why they dichotomised the following variables: maternal age, maternal BMI, birth weight at delivery, gestational age, Apgar score, postnatal EPDS. Whereas this is useful to represent the data, doing so they are likely to lose nearly a third of the information (see Altman & Royston, BMJ 2006).

• Out of the n=84 women, how many women were depressed in the second and in the third trimester?

• Would also be interesting to know how many women were diagnosed with minor and major depression as these have different risk factors (see Marchesi, Bertoni & Maggini, Obstet Gynecol, 2009). Did the authors found the same results when splitting the predictor in these two groups?

• When defining the confounding variables is not clear how the authors selected eight variables out of the seventeen available as covariates. A reference would be needed here. Especially considering that they excluded alcohol use from the covariates but in the discussion they state that “increased risk behaviours such as alcohol use and smoking which may ultimately affect the foetal intrauterine growth”. Which of the available variables in Table 1 were associated with the selected outcomes in Table 2?

• Following the previous comment, did the authors explore the possible interactions between the predictors? For example does the alcohol mediate the association between antenatal depression and low birth weight? Does any of the known risk/protective factors associated with post-natal depression interact in the association between antenatal depression and the EPDS score?

• It’s not clear to me why they used point-biserial correlations “to measure the strength and direction of the association between antenatal depression and continuous outcomes such as infant’s weight and height at six weeks postdelivery” but not with gestational age and weight at birth. Would also be interesting at least to know whether they found an association between antenatal depression and birth weight and gestational age as continuous variables. Also what’s the difference between point-biserial correlations coefficients and the beta in a linear regression?

• Including so many predictors as in the multivariate logistic regression might results in multi-collinearity issues. Did the authors test for the association among the predictors? Especially when dichotomising the covariates it is possible that some subgroups have in fact zero subjects (e.g., in a 2 by 2 table how many women have chronic illnesses diagnosed during the pregnancy but no chronic illnesses before the pregnancy?). I’m asking because this might affect the p-value.

• I think I don’t understand the meaning of the sentence “The low uptake of exclusive breastfeeding could be due to cultural barriers that young mothers face when trying to implement this”. Could the authors pleas spell out this part of the discussion?

Minor points

• In table 4 the asterisks are missing for the association between HIV status and assisted delivery and infant illness at 6 weeks. Also “predictable” might be changed into “predictors”.

• I’m not a native English speaker but I spotted a couple of typos (e.g. “Maternal postnatal depressive symptoms at six weeks postdelivery post-delivery” and “recorded in the baby’s medical booklet Research team members checked”). Also the last paragraph of the “Data collection procedure” seems redundant with the methods section. The authors should probably proofread the manuscript.

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Reviewer #1: No

Reviewer #2: Yes: Paolo Ossola

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PONE-D-21-18898R1Antenatal depression: Associations with birth and neonatal outcomes among women attending maternity care in Harare, ZimbabwePLOS ONE

Dear Dr. Kaiyo-Utete,

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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The authors have made several substantial changes to their manuscript. However, a new reviewer has suggested several areas for further clarification, especially regarding explanation of terms/concepts and limitations to the study design. In addition, paying attention to using causal language, only where the study does show causality; in all other cases, correlations/associations should be reported.

The reviewer recommends some grammar/style changes, such as not starting a sentence with "However". These types of comments can be changed or not at the authors' desire. 

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Please submit your revised manuscript by Jun 10 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Michael Wells

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Partly

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: Thank you for the opportunity to review this important manuscript. This study aimed to assess the associations between antenatal depression and birth and neonatal outcomes among women attending maternity care in Harare, Zimbabwe- a location where this type of assessment has not been done prior. While I think the authors made some adjustments based on prior reviewers, there are still major revisions that need to be made before this would be considered publishable.

1. Abstract: this study looks at associations. I would rephrase/remove talk of causality in the introduction. Few studies have been done in Zimbabwe, which is a fine justification for the study.

2. Citation 20 needs full brackets in the text. It is missing

3. Introduction: do not start a paragraph with “However”—suggest rewriting second and third paragraphs to help with flow. Very much like the last paragraph in the introduction setting up the study- just need a bit of a cleaner intro and segue into that study purpose paragraph.

4. Exposure: You say “SCID-IV is administered by trained mental health professionals” and then a few sentences later “Here, trained study psychiatrists administered the SCID-IV during data collection.” You do not need both.

5. Outcomes-birth outcomes: Is medical booklets correct term? This isn’t used in the USA. Please elaborate.

6. Missing a period in the sentence here “Infant’s weight and height were measured routinely by the attending midwife or nurse and recorded in the baby’s medical booklet [ADD PERIOD] Research team members checked the…

7. If this was part of a validation study. Why is Pre and postnatal depression measured using different tools?

8. Why was prior perinatal depression not included as a covariate. It is the MOST predictive factor for future perinatal depression.

9. All statistical analysis was done in STATA version 14[ADD PERIOD]

10. Be consistent with how numbers are formatted.

11. Table 1. What does “Negative life event in the past one year” mean? How was it measured?

12. Please put the antenatal depression findings in table 1. IT will be easier for readers.

13. Please add unit to weight.

14. Table 3. Remove statistical significance * from birthweight and remove the 1’s from the comparison group under Unadjusted OR

15. Table 4 is really hard to read. Why are all outcomes included even though most were not associated with the outcome in the unadjusted model? I would suggest using a 0.2 cutoff and only showing birthweight, breastfeeding at 6 weeks, and postnatal depression.

16. Agree with prior reviewer- please include tables with demographics and outcomes from babies whose mothers were antenatally depressed vs. those not. The frequencies and counts would be valuable. Differences in demos would also be valuable to assess.

16. Are there differences in the 2 clinics? I would suggest added the clinic to the model in case there are.

17. Discussion: “One possible explanation for this association is that mothers with depression have reduced cognitive function, which may lead to poor maternal nutrition, poor health seeking behaviours and increased risk behaviours such as alcohol use and smoking which may ultimately affect the

foetal intrauterine growth.”—this is a really big and bold statement with a lot of maternal blame. Could there not be other reasons for low birth weight in a developing country?

18. Discussion: It is stated that screening tools overestimate the prevalence of depression but they used a screening tool for postnatal depression.

19. Conclusion: Universal screening for antenatal depression is recommended by the American College of Gynecologist. May need to be added to WHO’s recommendations.

20. From prior reviewer—please correct parity description in the tables- Participants can be either primipara or multiparas

21. If the authors believe the lack of statistical significance between depression and certain outcomes may be due to the fact that most participants were diagnosed with minor depression—assess this. You have the data!

22. The fact that depression was only measured once during pregnancy is a major limitation.

23. IN the response to reviewers it is stated that multicollinearity was assessed. Please state that in the methods and results.

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Reviewer #3: No

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Antenatal depression: Associations with birth and neonatal outcomes among women attending maternity care in Harare, Zimbabwe

PONE-D-21-18898R2

Dear Dr. Kaiyo-Utete,

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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Additional Editor Comments (optional):

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