PONE-D-21-10270

Factors associated with preterm birth among mothers who gave birth at public Hospitals in Sidama regional state, South East Ethiopia: Unmatched case control study

PLOS ONE

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Reviewers' comments:

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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: Partly

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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Reviewer #1: Yes

Reviewer #2: Yes

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

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Reviewer #1: Yes

Reviewer #2: No

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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: In this manuscript, the authors investigated factors associated with preterm birth at public hospitals in Sidama regional state, South-east Ethiopia, 2020. They found that risk of PTB is increased in women living in rural areas, with no ANC follow-up, have UTI, PIH, chronic medical problems, low birth spacing, and suffer with physical violence during pregnancy.

The study is well designed, the results are clear, manuscript is well written and clinical significance is high. But following comments/questions should be addressed prior to acceptance.

1. Materials and Methods: The authors described that the definition of PTB is delivery before 37 completed gestational weeks, but the control group of this study consisted of women who delivered at 28-36 weeks of gestation. Is there any reason for excluding extremely early PTB at less than 28 weeks of gestation?

2. Materials and Methods: Calculating gestational age correctly is most important for determining cases and controls (preterm and term birth). In this study, gestational age was confirmed by LMP or early ultrasound record. However, calculating gestational age by LMP may not be correct in many women (especially when their periods were irregular or very long), and recall bias may occur. Since, antenatal check was not done in 30% and 13% of the cases and controls, there may be misclassification bias. This issue should be included in the Discussion section.

4. Discussion: The authors stated that the reason for higher risk of PTB in rural residents may be hard physical works like farming. Is there any evidence for this explanation?

5. The strengths and weaknesses of this study should be discussed in the Discussion section.

Minor issues

1. Introduction, first line: what is ‘tremidinous’? Is it ‘tremendous’?

2. What is MDG 4? The full term of the abbreviations should be presented.

3. Figure 2 is not shown.

Reviewer #2: Review PONE-D-21-10270

Factors Associated with Preterm Birth among Mothers Who Gave Birth at Public Hospitals in Sidama Regional State, South East Ethiopia: Unmatched Case Control Study

This study investigates risk factors of preterm birth in the Sidama region of south east Ethiopia with one of the highest prevalence of preterm births in the world. The aim is to provide insight into risk factors of preterm birth in the region to enable comparison with other nations research on preterm birth.

The authors performed a facility based unmatched case-control study. Preterm birth was defined as singleton live birth between 28 and 36 completed weeks of gestation. Singleton live birth between 37 and 41 completed weeks of gestations were included as controls.

The following aspects were investigated for inclusion as potential risk factor of preterm birth:

Maternal socioeconomic-factors: Maternal age, marital status, residence (Urban or rural), education, household income, number of children. Obstetrics related characteristics: Gravidity, birth interval of this pregnancy, follow up from antenatal care service, first antenatal care started, number of antenatal care, place of ANC follow up, danger sign of pregnancy advised, history of preterm, pregnancy-induced hypertension, ante partum bleeding, premature rupture of membrane. Pre-existing medical problems: MUAC, maternal height (short stature), Hgb of mother at booking in mg/dl, Chronic medical problem, UTI, Sexually transmitted infections, HIV status of Mother. Neonate: Birth defects, sex of neonate, birth weight.

The authors found several factors significantly associated with preterm birth: Rural resident (AOR: 2.034; 95%CI: 1.242, 3.331), no antenatal care service utilization (AOR: 2.516; 95%CI: 1.406, 4.503), pregnancy-induced hypertension (AOR: 2.870; 95%CI: 1.519, 5.424), chronic medical problem during pregnancy (AOR: 2.507; 95%CI: 1.345, 4.676), urinary tract infections (AOR: 3.023; 95%CI: 1.657, 5.513), birth space less than 2 years (AOR: 3.029; 95%CI: 1.484, 6.179), and physical intimate

violence (AOR: 2.876; 95%CI: 1.534, 5.393).

Major

Have cases and controls been selected to obtain equal frequencies of male / female neonate sex in cases and controls? The equal male frequency of 58.5% in cases and controls seems to be somewhat unexpected if controls are drawn by random. Could the authors please see if this is due to method or comment on this?

The discussion could be improved by including something on covariation of risk factors and elaborate on how combinations of these could be less or more important in this region of high prevalence of preterm birth especially compared to in other countries. See several points in discussion below.

Minor

Abstract

In sentence informing about software applied it should be EpiData without hyphen:

“Data were entered using Epi-data version 3.1 and exported to SPSS version 20 for analysis.

Introduction

At page 4 (top section) the authors mentioned some other studies in the field, are any of those possible to include as sources?

“But, in Ethiopia, few studies were conducted on risk factors associated with preterm birth and showed contradicting findings across different geographical settings and different periods.”

Results

Obstetrics related characteristics

Gravidity is categorized into equal to or above 5 and less than 5 which is less informative than primiparous compared to multiparous, is it enough available data to get information on primiparous in the study?

Variable name should be ‘first antenatal care started’ instead of ‘fist antenatal care started”.

Based on frequency of pregnancy-induced hypertension have these pregnancies been assessed for preeclampsia?

Pre-existing medical problems related characteristics

On page 10 the authors use the category ‘chronic medical problems’ without describing in further detail. “Chronic medical problems were diagnosed among 39(28.9%) of the cases and 26(9.6%) of the controls group.”

Is it possible to include some examples of which chronic conditions or medical problems that would classify into this variable?

In table 3 describing maternal pre-existing medical problems, height has an above and below 150 cm threshold, could the authors describe this variable more, is in in relation short stature from to malnutrition?

Fetal related characteristics

See major concern above on equal neonatal male frequency in cases and controls

Factors associated with preterm birth

Table 5, variable pregnancy-induced has a misprint in AOR 2.870(1..519, 5.424)

Discussion

The authors include comparable studies in discussion. Include in the discussion how the results compare to published data also where they deviate. Are there some results that should be expected to associate with preterm birth that show less association than expected in these results?

Please discuss if the results indicate a less prominent role of malnutrition as a risk factor of preterm birth in the region.

For instance, in the data material, the frequency of birth defects seems high. Could many of these be associated to malnutrition (like cleft palate) in a sense that birth defects from malnutrition, even high, is not a prominent risk factors of preterm births in the region? Could this be interpreted in relation to many of the maternal pre-existing medical problems that are malnutrition related and not prominent drivers of preterm birth in the dataset. Could the authors comment on malnutrition and nutritional aspects in relation to preterm birth in the region from the data in the study?

If possible, could the authors elaborate on probable covariation of some of the included risk factors? Is it possible to observe any interaction between rural residency and physical violence or between rural residency and use of antenatal care? Considering rural facilities on sanitation and access to clean water, could possibly rural residency and factors as PPROM and UTI show interaction? Place of ANC follow up seems to indicate some association to rural residence as well.

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Reviewer #1: No

Reviewer #2: No

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Factors associated with preterm birth among mothers who gave birth at public Hospitals in Sidama regional state, South East Ethiopia: Unmatched case control study

PONE-D-21-10270R1

Dear Dr. Fetene,

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):

Dear Author,

the manuscript has been well worked through and the reviewers comments to the manuscript have been followed up in a very thorough manner.

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 #1: All comments have been addressed

Reviewer #3: All comments have been addressed

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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 #1: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

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 #1: Yes

Reviewer #3: Yes

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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 #1: Yes

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 #1: The authors revised the paper well, and I have no more comment. Although there are are some minor technical errors (e.g., capital/small letters, spaces etc.), the paper now seemed to be suitable for publication.

Reviewer #3: In this manuscript, the authors investigated factors associated with preterm birth at public hospitals in Sidama regional state, Southeast Ethiopia, 2020. The study is well designed, the results are clear, the manuscript is well written and clinical significance is high. After reviewing the other comments from the editors and reviewers, allow me to make a few points.

- Consider including risk factors in keywords

- I understand that ANC (Antenatal care follows up), but I cannot identify that it was named for the first time with its respective acronym before page 12

- In the first paragraph of page 12 the acronym PIH appears, but I cannot identify if it was previously named with its meaning either.

- In the discussion I see that most of the studies that the authors took as a comparison are from the same region or geographic area, as a recommendation they suggest that they take into consideration, for example, developing Latin American countries where they can find very similar results to those studies and would give it a more inclusive character

- In most countries where access to health services is limited and where prenatal care is not started early, determining gestational age can be a real problem. That is why having a first trimester ultrasound is a reasonable alternative for those women who do not remember the date of their last menstrual period, or it is not reliable. While it is true that according to the recommendation of the American College of Obstetricians and Gynecologists in its Committee Opinion No 700 (Committee Opinion No 700: Methods for Estimating the Due Date, Obstetrics & Gynecology: May 2017 - Volume 129 - Issue 5), cited by the authors state that “ A pregnancy without an ultrasound examination that confirms or revises the EDD before 22 0/7 weeks of gestational age should be considered suboptimally dated”. The same committee also establishes that “Ultrasound measurement of the embryo or fetus in the first trimester (up to and including 13 6/7 weeks of gestation) is the most accurate method to establish or confirm gestational age.” Therefore, the authors could consider putting as a limitation that in sonographies after 14 weeks, the margin of error in calculating gestational age could exceed 7 days.

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Reviewer #1: No

Reviewer #3: No