Prevalence of Labor Induction,its Indication,and Feto-Maternal Outcomes in Ethiopia: A Systematic Review and Meta-Analysis

Abstract

Labor induction (IOL) is a common obstetric intervention to stimulate uterine contractions before the spontaneous onset of labor, with the goal of achieving vaginal delivery. It is indicated for various reasons, including post-term pregnancy, premature rupture of membranes (PROM), maternal medical conditions, and fetal growth restriction. This study aims to evaluate the prevalence of labor induction, its indications, and the associated maternal and fetal outcomes in Ethiopia. A comprehensive search for relevant articles was conducted using widely recognized databases such as Google Scholar, Cochrane, PubMed, HINARI, Web of Science, African Online, and institutional repositories from Ethiopian universities. Data were extracted using the standard format provided by the Joanna Briggs Institute. The Cochran Q test and I² statistics were employed to assess the heterogeneity of the studies. Publication bias was evaluated using a Funnel plot and Egger’s test. A Forest plot was used to present the pooled prevalence of labor induction in Ethiopia. This systematic review and meta-analysis revealed that the overall pooled prevalence of induction of labor in Ethiopia was 14.4% (95% CI: 11.09-17.70; I² = 95.7%, P < .01). The primary indications for labor induction included premature rupture of membranes (33.91%), intrauterine fetal death (8.8%), intrauterine growth restriction (4.85%), post-term pregnancy (21.49%), oligohydramnios (12.2%), and hypertensive disorders (30.7%). Maternal complications related to induction of labor included postpartum hemorrhage (9.47%), cesarean section (28.68%), instrumental delivery (18.82%), and vaginal tears (14.45%). Adverse fetal outcomes included low Apgar scores at 1 min, fetal death, and neonatal intensive care unit (NICU) admission, with respective rates of 48.2%, 6.11%, and 15.5%. According to this systematic review and meta-analysis, the estimated overall prevalence of induction of labor in Ethiopia is 14.4%. The indications for induction of labor include premature rupture of membranes (PROM), intrauterine fetal death (IUFD), intrauterine growth restriction (IUGR), post-term pregnancy, oligohydramnios, and hypertensive disorders. Maternal complications of labor induction include postpartum hemorrhage (PPH), cesarean section, instrumental delivery, and vaginal tear. Adverse fetal outcomes associated with induction of labor include a low first-minute Apgar score, fetal death, and admission to the neonatal intensive care unit (NICU). Careful consideration and balancing of risks are essential when deciding to induce labor. Additionally, clear national protocols and follow-up on induction of labor are crucial to mitigate these risks. Registration number: reviewregistry2051.

Keywords

Induction of labor indication fetal outcomes maternal outcome Ethiopia

Introduction

Intrapartum interventions refer to medical procedures and actions taken during labor and childbirth to monitor, assist, or manage the labor process, ensuring the safety and well-being of both the mother and the baby.¹ These procedures are usually carried out in hospital settings by a team of healthcare professionals including obstetricians, midwives, and nurses. Their aim is to address any complications, facilitate labor progress, manage pain, and optimize health outcomes for both mother and baby. Examples of these interventions include continuous fetal monitoring, artificial rupture of membranes (amniotomy), administration of oxytocin to induce or accelerate labor, epidural anesthesia for pain relief, assisted vaginal delivery using forceps or vacuum, and cesarean section delivery when medically necessary.^2,3

Induction of labor (IOL) is an obstetric intervention used to stimulate uterine contractions before spontaneous labor begins. This process aims to achieve a vaginal birth and can be performed for various reasons including post-term pregnancy, premature rupture of membranes (PROM), maternal pharmacological interventions, and fetal growth restriction.^4
-6 Induction methods include both medication and mechanical approaches. Medications such as prostaglandin or oxytocin are used to ripen the cervix and stimulate uterine contractions, while mechanical methods involve manual sweeping of the amniotic membrane or amniotomy (breaking the water), which leads to the release of hormones that may initiate labor.^7,8

However, IOL comes with certain maternal and fetal medical risks. These risks can vary from minor to severe and may necessitate additional medical attention or intervention. Potential risks include failed induction, overstimulation of the uterus (excessive contractions), postpartum hemorrhage, uterine rupture, increased cesarean section rates, fetal distress, maternal infection, cord presentation, and prolapsed umbilical cord, as well as maternal and fetal death.^7,9 Therefore, healthcare providers should adhere to national and WHO guidelines for indications and accurately assess maternal and fetal conditions before inducing labor to minimize the risk of complications for both mother and baby.¹⁰

In the United States, the incidence of IOL was 27.5%, while in the United Kingdom, it was approximately 31.9% for the year 2018 to 2019, and notably higher at 43.6% in Australia.¹¹ Research in the USA has shown that women undergoing IOL are more likely to deliver via cesarean section (35.9%) compared to those in spontaneous labor (18.9%).¹² Conversely, in Ethiopia, the reported rate of failed induction is 23.58%, leading to increased risks of fetal distress and cesarean section.¹³ Given these statistics, it is crucial to assess the prevalence of IOL, its determinants, and its impact on maternal and fetal health in Ethiopia. Understanding these factors is essential for informing policy decisions and interventions to improve obstetric practices and outcomes in the country. Therefore, this proposal aims to investigate the prevalence of IOL, its associated factors, and feto-maternal outcomes across Ethiopia.

Research Questions

What is the prevalence of IOL in Ethiopia?

What are the indications of IOL in Ethiopia?

What are the fetal outcomes of IOL?

What are maternal outcomes of IOL?

Methods

This study was registered post-study at Research Registry: registration number reviewregistry2051.

Study Setting

To do this systematic review and meta-analysis, the studies conducted in Ethiopia were incorporated.

Search Strategy

The appropriate articles regarding the prevalence of IOL, indications and Feto-maternal outcomes in Ethiopia were systematically searched form 15/04/2024 to 30/04/2024 GC using various international databases including Google Scholar, Cochrane, PubMed, HINARI, Web of Science, Scopus, as well as African Journals Online. The search strategy was structured according to the PICO (Population, Intervention, Comparison, Outcomes) format. These are “labor of induction,” “oxytocin,” “prostaglandin,” “mechanical induction,” “aminiotomy,” “artificial rupture of membrane,” “fetus,” “fetal distress,” “fetal death,” “associated factors,” “adverse fetal outcomes,” “adverse maternal outcomes,” “prolonged labor,” “hemorrhage,” “infection” “cesarean section,” “uterine hyperstimulation,” “precipitated labor,” “ placenta abruption,” “maternal death,” “Ethiopia.” The MeSH engine term that will used for search include “Induction of labor,” OR “Medical induction” [MeSH], OR “Oxytocin,” OR “prostaglandin,” OR “Mechanical induction,” [MeSH], “Aminiotomy,” OR “Artificial rupture of membrane,” “Adverse fetal outcomes,” [MeSH], OR “Fetus,” OR “Fetal distress,” OR “Maternal death,” “Adverse maternal outcomes,” [MeSH], OR “Infection” OR “Cesarean section,” OR “Uterine hyper-stimulation,” OR ‘’Precipitated labor,” OR ‘’Placenta abruption,” OR ‘’Uterine rapture,” OR ‘’Postpartum hemorrhage (PPH),“ “Maternal death,” OR “Associated factors,” [MeSH] “Post-term pregnancy,” OR “Hypertensive disorder during pregnancy,” OR “Pre-labor rupture of fetal membrane.”

Eligibility Criteria

Inclusion and Exclusion Criteria

The articles reviewed the prevalence of IOL, its indications, and maternal and fetal outcomes in Ethiopia, pooling the results together. The relevance and quality of the selected articles were assessed using the updated standard guidelines for reporting systematic reviews. Articles with a low risk of bias, according to the standard rating, were included. Additionally, only articles and literature in English were considered. Articles lacking complete abstracts or texts, or those reporting outcomes outside the area of interest, were excluded.

Quality Assessment

This systematic review and meta-analysis included a quality appraisal of the studies using the Joanna Briggs Institute (JBI) checklist for an analytic cross-sectional study.¹⁴

This checklist comprises 8 items, including clear inclusion criteria in the article, an appropriate description of the study subjects and setting, validity and reliability of outcome measurements, proper description of objectives and standard criteria used, identification of confounders during data analysis, use of an appropriate strategy to handle confounders, reliability and validity of outcome measurements, and relevance of the statistical analysis used. Each article and piece of literature underwent independent evaluation by the authors. Any discrepancies or disagreements that arose during this process were addressed and resolved through discussion among the authors. Whenever necessary, the author facilitated the resolution of disagreements to ensure a consensus was reached.

Articles scoring 50% and above on the JBI checklist, indicating low risk, were considered appropriate for inclusion in the final analysis. This rigorous quality assessment process ensures that only studies meeting predefined quality criteria were included, enhancing the reliability and validity of the systematic review and meta-analysis findings.

Data Extraction

Data extraction was entail transferring retrieved datasets to EndNote version X8 software to eliminate duplicates before migrating to a Microsoft Excel spreadsheet. Subsequently, data was independently extracted using a standardized JBI data extraction format.

Measurement of Outcome

This systematic review and meta-analysis had 4 measurement outcome variables. These measurements of the outcome variables were the prevalence of induction, associated factors, fetal outcomes, and maternal outcomes. We focused on feto-maternal outcomes not neonatal outcomes of labor induction because of the lack of data.

Induction of labor (IOL): is defined as initiation of the uterine contraction in women after 28 weeks of gestation for different reasons.^2,5

Indications for labor: These are defined as the factors that result in the IOL including post-term pregnancy, hypertensive disorder during pregnancy, and pre-labor rupture of the fetal membrane.¹²

Fetal outcomes: are defined as the complications of the new-born following IOL including non-reassuring fetal heart rate (NRF-HPR), Inter uterine fetal death (IUFD), low Apar score, admission to NICU.¹⁵

Maternal outcomes: are defined as complications of the mother after IOL including precipitated labor, placenta abruption, uterine rupture, postpartum hemorrhage (PPH), and maternal death.^15,16

Data Analysis

To assess publication bias, we used both a Funnel plot and Egger’s regression tests.¹⁷ Additionally, we evaluated heterogeneity across studies, considering each study’s impact on the overall findings of the systematic review and meta-analysis. Heterogeneity was assessed using I-squared statistics and the Cochrane Q-test.¹⁸ A weighted inverse variance random-effects model was used for the pooled analysis. Data analysis was performed using Stata v.14 statistical software. The final results of the analysis were presented in forest plot format and tables. The pooled point prevalence of labor induction was reported along with a 95% confidence interval (CI), providing a comprehensive overview of the findings.

Result

Literature Search Result

Characteristics of the Included Studies

The search was conducted using various databases, including PubMed, Science Direct, Web of Science, Google Scholar, HINARI, African Journals Online, and other gray and online repositories of universities in Ethiopia. A total of 2270 articles were accessed and retrieved (Figure 1; Table 1). After removing duplicates using Microsoft Excel, 567 articles remained for further review of their titles and abstracts. Of these, 328 articles were excluded after reviewing their titles and abstracts. Consequently, 92 full-text articles were assessed for inclusion criteria, resulting in the exclusion of 56 articles. Ultimately, 18 studies met the inclusion criteria for the final systematic review and meta-analysis. All included studies in this review were cross-sectional studies conducted using systematic random sampling techniques.

Figure 1.

PRISMA flow chart of selection of studies to be included in systematic review and meta-analysis of prevalence of induction of labor, indication, and feto-maternal outcomes.

Table 1.

The Features of the Studies to Be Included in a Meta-Analysis of the Prevalence of IOL, Indication, and Feto-Maternal Outcomes in Ethiopia.

No	Authors	Study year	Study area	Study design	Sampling technique	Sample size	Prevalence	Quality
1	Rade et al¹⁹	2018	Tigray	Cross-sectional	Systematic	384	10.90%	Low risk
2	Mulualem and Assefa²⁰	2017	Amahara	Cross-sectional	Systematic	319	-	Low risk
3	Demissew and Mesfin²¹	2020	Addis Ababa	Cross-sectional	Systematic	339	-	Low risk
4	Abdulkadir et al.²²	2016	Oromia	Cross-sectional	Systematic	340	22.40%	Low risk
5	Girma et al²³	2016	Oromia	Cross-sectional	Systematic	280	-	Low risk
6	Assemie et al²⁴	2023	Amahara	Cross-sectional	Systematic	411	-	Low risk
7	Tsega²⁵	2019	Southern Ethiopia	Cross-sectional	Systematic	294	20.40%	Low risk
8	Mohammed et al²⁶	2021	Central Ethiopia	Cross-sectional	Systematic	8000	-	Low risk
9	Deressa et al²⁷	2018	Addis Ababa	Cross-sectional	Systematic	181	33.90%	Low risk
10	Debele et al²⁸	2021	Amahara	Cross-sectional	Systematic	484	-	Low risk
11	Shiferaw et al²⁹	2020	Tigray	Cross-sectional	Systematic	3834	9.00%	Low risk
12	Demssie et al³⁰	2020	Oromia	Cross-sectional	Systematic	379	-	Low risk
13	Beshir et al³¹	2021	Harari	Cross sectional	Systematic	717		Low risk
13	Dereje et al³²	2023	Addis Ababa	Cross-sectional	Systematic	778		Low risk
14	Mulualem and Assefa²⁰	2020	Amahara	Cross-sectional	Systematic	340	-	Low risk
15	Tsega²⁵	2014	Southern Ethiopia	Cross-sectional	Systematic	110	6.40%	Low risk
16	Shiferaw et al.²⁹	2022	Diredawa	Cross-sectional	Systematic	444	-	Low risk
17	Laikemariam et al³³	2023	Amahara	Cross sectional	Systematic	788	-	Low risk
18	Amare Ejigu & Shewangizaw Lambyo	2021	South West	Cross sectional	Systematic	441	-	Low risk

Prevalence of Labor Induction in Ethiopia

This systematic review and meta-analysis showed the overall pooled prevalence of IOL with a forest plot. Therefore, the pooled estimated of the prevalence of induction of labor was 14.4% (11.09, 17.70; I² = 95.7%, P < .01; Figure 2).

Figure 2.

Funnel plot test for publication bias of the labor induction in Ethiopia.

Publication Bias

To check publication bias a funnel plot was assessed for the asymmetry distribution of the IOL using visual inspection of the forest plot (Figure 3). Egger’s regression test showed a P-value of .023 which indicated the absence of publication bias.

Figure 3.

Forest plot of prevalence of labor induction with a corresponding 95% CI of 14 studies.

Indications of Labor Induction

This systematic review and meta-analysis identified various indications for IOL. These indications include PROM 33.91% (95% CI: 28.25, 39.56), IUFD 8.8% (95% CI: 5.26, 12.37), IUGR 4.85% (95% CI: 1.68, 8.02), PDP 21.49% (95% CI: 15.06, 27.93), oligohydramnios 12.2% (95% CI: 3.08, 21.34), and HDDP 30.7% (95% CI: 26.08, 35.31 (Table 2).

Table 2.

Indications of Labor Induction in Ethiopia, Systematic Review and Meta-Analysis 2024.

Indications of labor induction	Model	Status of heterogeneity	Prevalence (95% CI)	I² (%)	P-value
Premature rapture of the membrane	Random	Marked	33.91 (28.25, 39.56)	97.8	<.01
Intrauterine fetal death	Random	Marked	8.818 (5.26, 12.37)	94.0%	<.01
Intrauterine growth restriction	Random	Marked	4.85 (1.68, 8.02)	92.7%	<.01
Post-term pregnancy	Random	Marked	21.49(15.06, 27.93)	98.8%	<.01
Oligo hydraminos	Random	Marked	12.2 (3.08, 21.34)	90.8%	<.01
Hypertensive disorder	Random	Marked	30.7(26.08, 35.31)	97.5%	<.01
Fetal malformation	Random	Marked	3.32 (0.35, 6.29)	92.5%	<.01

Maternal Outcomes From Labor Induction

Regarding the outcomes of IOL in Ethiopia, there are various complications affecting delivering women. According to this systematic review and meta-analysis, the complications include postpartum hemorrhage 9.47% (95% CI: 3.34, 15.61), cesarean section 28.68% (95% CI: 23.31, 34.04), instrumental delivery 18.82% (95% CI: 6.02, 31.59), and vaginal tear 14.45% (95% CI: 7.2, 21.7; Table 3).

Table 3.

Maternal Outcomes of the Labor Induction in Ethiopia, Systematic Review and Meta-Analysis 2024.

Maternal complications of labor induction	Model	Status of heterogeneity	Prevalence (95% CI)	I² (%)	P-value
Post-partum hemorrhage	Random	Marked	9.47 (3.34, 15.61)	96.1%	<.01
Cesarean section	Random	Marked	28.68 (23.31, 34.04)	96.0%	<.01
Instrumental delivery	Random	Marked	18.82 (6.02, 31.59)	99.2%	<.01
Uterine rupture	Random	Marked	0.93 (0.65, 1.21)	0.0%	.644
Vaginal tear	Random	Marked	14.45 (7.2, 21.7)	85.5%	<.01

Fetal-Outcomes of the Induction of Labor

This systematic review and meta-analysis revealed that adverse fetal outcomes following IOL in Ethiopia include a low first-minute Apgar score 48.2% (95% CI: 15.99, 32.79), fetal death 6.11% (95% CI: 0.97, 11.26), and admission to the neonatal intensive care unit (NICU) 15.5% (95% CI: 9.56, 19.43; Table 4).

Table 4.

Fetal-Outcomes of the Labor Induction in Ethiopia, Systematic Review and Meta-Analysis 2024.

Fetal complications of labor induction	Model	Status of heterogeneity	Prevalence (95% CI)	I² (%)	P-value
Low first minute Apgar score	Random	Marked	48.2 (15.99, 32.79)	99.6%	<.01
Fetal death	Random	Marked	6.11 (0.97, 11.26)	96.1%	<.01
Admission to NICU	Random	Marked	15.5 (9.56, 19.43)	95.8%	<.01

Discussion

Maternal mortality remains a pressing global health challenge, with around 830 women dying daily from preventable causes linked to pregnancy and childbirth, predominantly in low-resource settings. The World Health Organization highlights stark disparities in maternal health services across Africa. Southern Africa achieves near-universal coverage of basic maternal health interventions, while in West Africa, approximately one-third of pregnant women lack access to antenatal care visits. This underscores the urgent need for improved access to skilled care before, during, and after childbirth, particularly in underserved regions.³⁴

According to this systematic review and meta-analysis, the prevalence of IOL in Ethiopia is 14.4% (95% CI: 11.09, 17.70, I² = 95.7%, P < .01). This rate is comparable to a study form Nigeria 11.5%.³⁵ However, other studies report higher prevalence rates of IOL, such as 39.5% in Southern India³⁶ and 33% in the United Kingdom.³⁷ Conversely, studies have shown lower prevalence rates, including 3.6% in India,³⁸ 8.94% in Nepal,³⁹ 4.4% in Africa and 12.1% in Asia from the WHO global survey,⁴⁰ 2.5% in Tanzania,⁴¹ and 8.0% in South Africa.⁴² The differences in prevalence rates may be attributed to variations in study areas, obstetric protocols, and practices.

Regarding the indications for IOL, this systematic review and meta-analysis identified several reasons for this obstetric intervention. These include premature rupture of membranes 33.91% (95% CI: 28.25, 39.56), intrauterine fetal death 8.8% (95% CI: 5.26, 12.37), intrauterine growth restriction 4.85% (95% CI: 1.68, 8.02), post-term pregnancy 21.49% (95% CI: 15.06, 27.93), oligohydramnios 12.2% (95% CI: 3.08, 21.34), and hypertensive disorders 30.7% (95% CI: 26.08, 35.31). These findings are supported by studies conducted in different parts of the world, including India,³⁸ Southern India,³⁶ and South Africa.⁴² These obstetric complications contribute to maternal and fetal morbidity and mortality, so women and fetuses presenting to healthcare facilities with these conditions have a higher likelihood of undergoing labor induction.

Even though labor induction is an obstetric intervention performed for specific indications to reduce maternal and fetal complications and death, it is not without risks to both the mother and the fetus. According to present study, maternal complications associated with IOL include postpartum hemorrhage (9.47%, 95% CI: 3.34, 15.61), cesarean section (28.68%, 95% CI: 23.31, 34.04), instrumental delivery (18.82%, 95% CI: 6.02, 31.59), and vaginal tear (14.45%, 95% CI: 7.2, 21.7). These results are supported by various studies, including those conducted in India,³⁸ the United Kingdom,³⁷ another study from India,⁴³ the WHO global survey in Africa and Asia,⁴⁰ Tanzania,⁴¹ and South Africa.⁴² During IOL, uterine contractions may be stronger and more frequent, and failed induction can lead to precipitated labor, instrumental delivery, postpartum hemorrhage, vaginal tear, and cesarean section.

Similarly, our study showed that IOL has its own adverse fetal outcomes, including a low first-minute Apgar score 48.2% (95% CI: 15.99, 32.79), fetal death 6.11% (95% CI: 0.97, 11.26), and admission to the neonatal intensive care unit (NICU) 15.5% (95% CI: 9.56, 19.43). These results are supported by studies conducted in India (3.52%),³⁸ Australia,⁴⁴ India,⁴⁵ the United Kingdom,³⁷ the WHO global survey in Africa and Asia,⁴⁰ and Tanzania (NICU admission 8.3%).⁴¹ Strong uterine contractions can hinder placental blood flow, prompting further obstetric interventions, which can exacerbate conditions and result in a low first-minute Apgar score, NICU admission, and fetal death.^46,47

Strength and Weakness of the Study

This systematic review and meta-analysis included all accessible studies that aligned with the objectives. However, drawing definitive conclusions about IOL, associated factors, and feto-maternal outcomes is challenging due to weaknesses in the documentation of obstetric interventions. Additionally, the articles included in this study were not representative of all regions of Ethiopia, potentially limiting the national applicability of the findings. In addition, post-study registration may have introduced bias to our results and is a limitation of this study.

Conclusion and Recommendation

This systematic review and meta-analysis found a 14.4% prevalence of induction of labor (IOL) in Ethiopia (95% CI: 11.09-17.70, I² = 95.7%, P < .01). Key indications include premature rupture of membranes (33.91%), hypertensive disorders (30.7%), and post-term pregnancy (21.49%). Maternal complications include cesarean section (28.68%), instrumental delivery (18.82%), vaginal tear (14.45%), and postpartum hemorrhage (9.47%). Fetal risks include low first-minute Apgar score (48.2%), NICU admission (15.5%), and fetal death (6.11%). Despite its necessity, IOL poses significant risks, requiring evidence-based protocols to minimize complications. So that it is important to develop clear, evidence-based IOL protocols aligned with WHO standards, tailored to Ethiopia’s healthcare context, use risk stratification tools to evaluate IOL benefits versus risks before induction, provide training on safe IOL practices and complication management and create a national registry to track IOL outcomes and improve data quality.

Supplemental Material

sj-docx-1-inq-10.1177_00469580251411644 – Supplemental material for Prevalence of Labor Induction, its Indication, and Feto-Maternal Outcomes in Ethiopia: A Systematic Review and Meta-Analysis

Supplemental material, sj-docx-1-inq-10.1177_00469580251411644 for Prevalence of Labor Induction, its Indication, and Feto-Maternal Outcomes in Ethiopia: A Systematic Review and Meta-Analysis by Zerihun Figa, Addisu Getnet Zemeskel, Asrat Alemu, Anteneh Gashaw, Aschalew Gossaye Ejigu, Nigatu Tilahun, Tesfaye Temesgen, Fikru Bedecha and Bereket Tesfaye Gebre in INQUIRY: The Journal of Health Care Organization, Provision, and Financing

Footnotes

Acknowledgements

We would like to thank Dilla University for its financial support.

Abbreviations

PROM: Premature rupture of the membrane; NICU: Neonatal intensive care Unit; IUGR: Inter uterine growth restriction; IUFD: Inter uterine fetal death; CI: Confidence Interval: OR: Odds Ratio; JBI: Joan Briggs Institute, EBIPC: Evidence-based intrapartum care practice; EBO: Evidence-based practice; Induction of labor: IOL; OCP: Obstetrics Care providers; SRMA: systematic review and meta-analysis; WHO: world health organization

ORCID iDs

Zerihun Figa

Tesfaye Temesgen

Author Contributions

Zerihun Figa, Tesfaye Temesgen, Bereket Tesfaye Gebre and Addisu Getnet Zemeskel: Conceived and designed the method, analyzed and interpreted the data. Asrat Alemu, Anteneh Gashaw, Nigatu Tilahun, Fikru Bedecha and Aschalew Gossaye Ejigu: materials, analysis tools, or data and wrote the paper.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Dilla University

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

All related data has been presented within the manuscript. The dataset supporting the conclusions of this article is available from the authors on request.

Supplemental Material

Supplemental material for this article is available online.

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