PONE-D-21-37354Measurement of symphysis fundal height for gestational age estimation in Low-to-Middle-Income Countries: A systematic review and meta-analysisPLOS ONE

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This work was supported by the Bill & Melinda Gates Foundation through grant OPP1130198. This work was conducted with support from Harvard Catalyst | The

Harvard Clinical and Translational Science Center (National Center for Advancing

Translational Sciences, National Institutes of Health Award UL 1TR002541) and

financial contributions from Harvard University and its affiliated academic healthcare

centers. ACL was supported by a grant from the Eunice Kennedy Shriver National

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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: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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3. 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 #2: Yes

Reviewer #3: Yes

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4. 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 #2: Yes

Reviewer #3: 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: The literature review is accurate with the according references.

The introduction is excellent.

The methodology is clean. The SR were previously registered and the appropriate guidelines were used.

The objectives were clear. The assessment of biases and the analyses (random effect) are correct.

The conclusion and the discussion are accurate and interesting.

The importance of the paper is high.

Reviewer #2: The authors are to be commended for a well-designed study and exceptionally well-presented paper.

The data, clearly presented, conveys the limitations of utilizing symphysis fundal height measurements as an accurate estimate of gestational age.

The tables that were provided may serve as an superb guide to researchers where dating of pregnancy is key and ultrasound not available.

Regional differences in sensitivity and specificity of SFH have previously been reported; the weight of evidence presented confirms that such differences are real.

A 6-week window of variability for accurate dating is suggested, generally well in excess of the time required to assess critical perinatal outcomes.

I have no suggested edits. This is an excellent and well-referenced paper that warrants publication.

Reviewer #3: Thank you for asking me to review this interesting article on measurement of symphysis fundal height for gestational age estimation

Measuring SFH is used as a first level screening test to identify fetuses with growth aberrations. In resource poor settings SFH is used (in women where LMP is not known and where ultrasound is not available) to estimate GA.

I have a number of comments:

1. As the authors outline, ultrasound is most accurate for GA assessment. But, when it comes to GA estimation based on measurement (whether ultrasound or SFH) there is an underlying fundamental flawed assumption: namely that every fetus of a certain measurement is of the same GA. This is clearly untrue, due to normal biological variation; measurement variability; the fact that growth restriction (or fetal overgrowth) will automatically result in an under-(or over-) estimation of GA, respectively. This findamental limitation needs to come through better, as does the fact that such growth aberrations, in particular poor fetal growth, are most common in underserved regions.

2. Originality: As the authors state, previous systematic reviews have assessed SFH measurement for fetal growth monitoring. There is a recent SR on SFH for GA estimation (Second and third trimester estimation of gestational age using ultrasound or maternal symphysis-fundal height measurements: A systematic review. Self et al. doi.org/10.1111/1471-0528.17123). That study also looks at ultrasound parameters and not restricted to LMIC settings. Therefore I think the current study is still of value, but should reference the study by Self et al.

3. The lack of a unified or strong method as the comparator for GA is an important limitation in my view. As the authors themselves state, GA is best determined by ultrasound. Therefore comparing SFH to BOE or LMP is of very limited value – we do not know what the actual GA is. Please discuss this limitation and consider restricting analysis or sensitivity analysis including only ultrasound based "actual" GA.

4. The rationale is unclear as to why studies from LMIC were only included. You state this was done “because SFH charts are more likely to be used for GA dating in LMIC settings, while in HIC, pregnancies are typically dated by ultrasound and SFH charts are used for fetal growth monitoring purposes”. Charts of SFH may be constructed for dating or growth monitoring (or both), but to me there is actually an advantage of assessing HIC charts – exactly because dating is “secure”. The best strategy would be accurately dated pregnancies with SFH from LMIC settings, which is provided by Intergrowth. Please justify better your decision or better still include sich studies.

5. I question the exclusion of studies including only healthy populations – why was this done? Surely you cannot replicate SFH studies everywhere? If you include pathological pregnancies or higher BMI variability, how does that increase external validity - it will always depend on the proportion of pathology in each sub-population; and the distribution of BMI in each subpopulation. And even then you will only achieve accuracy at population level, even with "customisation". You need to explain this difference in the paper.

6. A sophisticated analysis was undertaking grouping world regions, gold standard and “a priori differences in fetal size and rates of growth restriction between Africa and Asia"…. and the authors developed separate SFH models for Africa and Asia. To me this is an over-sophisticated analysis given the many limitations of the constituent studies. It ignores or at best is hampered by the fact that the methods in different contributing populations are different… including of measurement strategy, dating etc. Differences due to region could be due to many other differences within each region such as data collection, quality, bias in measurement, etc etc. You try to address this by ensuring “only ultrasound/BOE studies were included”. I think it would be better to take the few best studies and assess this, including only the ones with best dating strategy based on early ultrasound. I would suggest revising the analysis strategy, aldo given the poont 8 below.

7. Point 6 is particularly relevant when you compare to the INTERGROWTH-21st SFH - in African LMIC settings these were similar but in Asian LMIC settings they were lower than the African cohorts. It should be explored what are the reasons for this in particular as the data were driven by a single study from Bangladesh.

8. Finally, to me the biggest issues are conceptual:

You show that prescriptive SFH standards suggest a high prevalence of SFH <10% in resource poor settings - poor settings have high levels of FGR. This also means that using SFH would underestimate GA in these same populations where FGR or pregnancy morbidities are prevalent. This however goes back to my point (1) in this review: you cannot know in an individual woman whether growth restriction is present or whether the comorbidity has affected fetal growth. Hence, I fundamentally disagree with your assertion that “the proposed regional population-based reference SFH values are clinically relevant and important for GA estimation in LMIC settings” and that “regional population-based reference SFH charts or customized SFH charts may provide a relatively better estimate of GA than international SFH standards”. Such an approach may better estimate GA at POPULATION level, but it is NOT useful clinically for the care of INDIVIDUAL women because you do not know the fetal size in the particular mother! You rightly caution, that “GA estimates should still be interpreted with a prediction window of ±6 weeks”. But in truth, this renders such a method pretty ineffective: Such accuracy can be achieved at clinic level by finding the most common GA women attend (eg if most women first attend at 24 weeks you can simply label each woman as being 24 weeks pregnant, this will work similarly). If it is a really bad method then say so, do not give clinicians the poor excluse to continue with poor practice!

You cannot have it both ways: on the one hand saying: “look our methods of regional charts are very good” and on the other hand saying “but actually all methods are bad”. Nail your colors to the mast: in my view the "mast" is the right one in the conclusion of your abstract, ie “SFH is inaccurate for estimating GA and should not be used for GA dating” – leave it there! “...whenever possible” is superfluous. What you have really shown is that SFH for GA estimation is inadequate care for vulnerable populations of pregnant women and should be abandoned. Only with such uncontroversial strong recommendations will we make progress… leaving a window open will always result in inadequate public health investment: the narrative will be “no we do not need ultrasound, CC Lee says we need more relevant SFH charts”, neglecting the +/- 6 week accuracy.

Do not undesetimate your power to shape policy on the ground, make the right decision! I would advise to change the narrative.

Minor comment:

I was unable to locate ref 2 “Intergrowth. INTERGROWTH-21st International Fetal and Newborn Growth Standards for the 21st Century”. Perhaps this should be the relevant Intergrowth website, if so please add this and the access date, or is it a paper you are referring to?

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Measurement of symphysis fundal height for gestational age estimation in low-to-middle-income countries: A systematic review and meta-analysis

PONE-D-21-37354R1

Dear Dr. Lee,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Simone Garzon

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #2: 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 #2: Yes

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

Reviewer #1: (No Response)

Reviewer #2: 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 #2: 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 #2: 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 addressed most of the concerns.

The rules for SR and MA have been adequately followed.

The originality and interest of the paper are important.

Reviewer #2: This well written paper is a systematic review describing measurements of symphysis fundal height (SFH) for gestational age estimation in low and middle-income countries. The systematic review included 37 (of 1,003 studies identified) 30 of which provided data for Africa and South Asia.

The overall “take-away message” for this meta-analysis is that measurement of symphysis fundal height is not a good tool for estimating gestational age. The article reinforces the importance of obtaining early ultrasound for assessment, where such knowledge can impact clinical management.

Nineteen different measurement techniques were noted among the > 33,000 participants. The sensitivity and specificity of SFH was found to be lower than other commonly used assessment tools.

The “one cm – one week rule” was found not to be accurate and SFH measurements in Asians was consistently lower for the same period of gestation than among women in Africa.

While it would have been helpful to determine at what time in pregnancy such measurements had been obtained, the poor predictive value of such measurements in LMICs would suggest that these not be primarily used in the management of patients. However, data presented will be helpful in further research initiatives related to pregnancy dating.

I have no edits or corrections. This paper is worthy of publication.

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Reviewer #1: No

Reviewer #2: No

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