Infants born at 29–36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA).N = 133) born 29–36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBFi) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMROi2). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA.Preterm infants (i (p < 0.0001) and CMROi2 (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBFi, and CMROi2 from birth to TEA were not associated with neurological examination at TEA.Steeper increases in CBFi and CMROi2 from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF Infants born between 29 and 36 weeks of gestational age (GA) represent the majority of preterm births , yet deti) (i2). This technique was previously used to monitor early brain development in preterm infants . NIRS has the potential to identify infants at higher risk of neurodevelopmental impairment as early as in the neonatal period . Combinii) , respect infants ,b, 2016, infants . Previou infants , as wellactivity .i and CMROi2  and acts in accordance with Quebec and Canada laws, and the Code of Federal Regulations in the USA. Parental written informed consent was obtained for each patient.This is a single-center prospective observational cohort study at Sainte-Justine University Hospital Center, a tertiary referral hospital in Montreal, Canada. From August 2018 to April 2020, we consecutively recruited infants born between 29 and 36 6/7 weeks GA who were admitted for at least 48 h at the neonatal intensive care unit. Exclusion criteria were major chromosomal anomaly and congenital malformations, moderate to severe hypoxic ischemic encephalopathy, and neonatal stroke, as these infants already benefit from neurodevelopmental follow-up in specialized clinics; moribund infants; and infants under child protection services due to consent issues. The study (#2019-1936) was approved by the institutional review board of the 2, %) was measured from preductal pulse oximetry at an upper limb. We used hemoglobin concentration in blood  measured for clinical purposes throughout the hospital stay.Parents completed a questionnaire for demographic data. Perinatal and neonatal characteristics were retrieved from medical charts. Peripheral arterial oxygen saturation  . The sysBrain monitoring was performed from the first week of age to TEA, defined as between 37 and 40 weeks of post-menstrual age. The number of monitoring sessions varied between neonates and depended on GA and the length of hospital stay. Each session required 15–20 min. For each patient and FDNIRS-DCS parameter, temporal change was calculated by the difference between the value at (or near) TEA and the value measured at the first visit normalized by the temporal period that separated the two measurements (in weeks).2, %) was calculated by the ratio between oxyhemoglobin  and total hemoglobin  derived from FDNIRS signals. OEF was defined by the ratio between the arterio-venous O2 saturation difference (SpO2 – SvO2) and SpO2, where SvO2 was estimated via an arterial:venous contribution ratio of 0.25:0.75 as in previous studies . These calculations were performed in MATLAB .Absolute cerebral oxygen hemoglobin saturation  (Q = 7.224)  was performed by a trained member of the research team blinded to the medical history and FDNIRS-DCS results. The ATGNA is a standardized 5 min exam consisting of 35 items evaluating head growth, cranial sutures, alertness, passive muscle tone of the limbs and axis, and axial motor activity. Results are synthesized in clusters to provide a final categorization: optimal  exam defined as no neurological sign, or non-optimal  exam with presence of mild/moderate or severe neurological signs . Previou = 0.92) , stabili= 7.224) , and abi= 7.224)  and subo= 7.224) .2 measures were associated with the neurological examination by performing logistic regression models. In sensitivity analyses, we assessed the association of FDNIRS-DCS temporal changes measured on the left and right frontal regions with GA at birth and with neurological exam at TEA using linear and logistic regression models, respectively. P-values of <0.05 were considered statistically significant, and analyses were conducted using SAS version 9.4 .Descriptive statistics are reported as means (standard deviations) and proportions. The association of FDNIRS-DCS first measure and temporal changes with GA at birth was assessed using univariate linear regression models. We further examined the effect of sex using multiple linear regression models. We performed logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between FDNIRS-DCS parameters and the neurological examination at TEA. Models for the relationship between FDNIRS-DCS parameters at first visit and neurological exam at TEA were adjusted for post-menstrual age at the time of measurement, as it did not systematically occur at the same post-menstrual age for each patient. We performed subgroup analyses stratifying by GA (29–32 vs 33–36 weeks GA) and by sex . We also examined how cerebral SOAmong 150 infants initially recruited, 133 completed the neurological assessment at TEA and were included in the study . Particii2 data at TEA were available in 90 patients, for CBFi in 92 patients, and for OEF in 98 patients. When considering FDNIRS-DCS temporal change, CMROi2 data were available in 71 patients, for CBFi in 74 patients, and for OEF in 93 patients. The average time between birth and consent was 4.13 days (SD = 2.21), and the average time between birth and first FDNIRS-DCS measurement was 4.88 days (SD = 2.94). Mean time interval between first and last FDNIRS-DCS measurements was 4.45 weeks (SD = 2.77).After data quality assessment of FDNIRS and DCS data separately, CMROi (p < 0.0001) and CMROi2 (p = 0.0003) were associated with higher GA at birth . In contrast, there was no significant association between CMROi2 and CBFi at first visit and GA at birth. The relationship between OEF first measurement and GA reached statistical significance , but the magnitude of association was very weak .Steeper increases in CBFat birth . Howeverery weak . In adju2 at first and last visits or temporal change in SO2 and neurological examination at TEA  and CMROi2  was significantly associated with higher GA at birth, but there was no association between temporal change in OEF and GA . Similar to our main analyses, there was no significant association with neurological exam at TEA, whether considering the temporal change in CMROi2 , CBFi , or OEF .In sensitivity analyses, models considering FDNIRS-DCS measurements on the left and right frontal regions yielded results that were comparable to our main analyses examining the middle frontal location. A steeper rise in CBFi2 and CBFi over time and increasing GA at birth. There was no association between FDNIRS-DCS parameters at TEA or temporal changes and the neurological examination at TEA. To our knowledge, this is the first study assessing the relationship between serial FDNIRS-DCS measurements of brain hemodynamics and oxygen metabolism and a standardized neurological examination at TEA in infants born between 29 and 36 6/7 weeks GA. These findings suggest that FDNIRS-DCS and the neurological exam may be complementary, informing on brain hemodynamics and metabolism and neurological status at TEA, respectively. These data highlight the need to further explore how FDNIRS-DCS could help identifying infants at high neurodevelopmental risk who would benefit from targeted intervention.In this cohort of 133 infants born between 29 and 36 6/7 weeks GA, there was a significant association between steeper rises in CMRO2 and OEF obtained in the first days of life are associated with later neurodevelopmental outcomes in infants born very preterm with inconsistent results. Two cohort studies of infants born before 32 weeks GA indicated that a lower cerebral SO2 in the first 72 h of life was associated with lower cognitive scores at 24 months CA  and supply (flow), and may therefore determine their independent contribution , in accordance with Quebec and Canada Laws, and the Code of Federal Regulations in the United States. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.GC-C, M-NS, MD, and TML conceived and designed the study. OB, RC, and MD contributed to the FDNIRS-DCS assessment. M-MG, MG, and TML performed the neurological examinations. CB contributed to the clinical data collection. GC-C and OL performed the statistical analyses with input from M-NS, MD, and TML. GC-C drafted the original manuscript with critical revisions from M-NS, AMN, MD, and TML. All authors contributed to the acquisition, analysis, and interpretation of data, read, and approved the final manuscript.


A birth companion is a simple and low-cost intervention that can improve both maternal and newborn health outcomes. The evidence that birth companionship improves labor outcomes and experiences of care has been available for many years. Global and national policies exist in support of birth companions. Many countries including Ethiopia, Kenya, and Nigeria have not yet incorporated birth companions into routine practice in health facilities. This paper presents the protocol for a trial that aims to assess if a package of interventions that addresses known barriers can increase the coverage of birth companions.This two parallel arm cluster randomized controlled trial will evaluate the impact of a targeted intervention package on scale-up of birth companionship at public sector health facilities in Ethiopia (five study sites encompassing 12 facilities), Kenya (two sites encompassing 12 facilities in Murang’a and 12 facilities in Machakos counties), and Nigeria (two sites encompassing 12 facilities in Kano and 12 facilities in Nasarawa states). Baseline and endline assessments at each site will include 744 women who have recently given birth in the quantitative component. We will interview a maximum of 16 birth companions, 48 health care providers, and eight unit managers quarterly for the qualitative component in each country.Ample evidence supports the contribution of birth companions to positive health outcomes for mothers and newborns. However, limited data are available on effective strategies to improve birth companion coverage and inform scale-up efforts. This trial tests a birth companion intervention package in diverse clinical settings and cultures to identify possible barriers and considerations to increasing uptake of birth companions. Findings from this study may provide valuable evidence for scaling up birth companionship in similar settings.Trial is registered with ClinicalTrials.gov with identifier: NCT05565196, first posted 04/10/ 2022. Ethiopia, Kenya, and Nigeria have experienced large increases in facility deliveries in the past decade. In Ethiopia, facility births increased from 11% to 2011 to 48% in 2019, in Kenya from 43% to 2008 to 61% in 2014 and in Nigeria from 23% to 2013 to 40% in 2018 –9.The presence of a birth companion during a woman’s labor and birth is a simple and low-cost intervention that can improve both maternal and newborn health outcomes. This kind of support has been referred to by several different names: companion of choice at birth; continuous support during childbirth, labor companion, and emotional support during birth . A birthA 2013 Cochrane systematic review of 21 trials showed that women who had continuous presence and support during labor or labor and birth were more likely to have a spontaneous vaginal birth, and report satisfaction with the care they received. Having continuous support during labor was also associated with shorter labor, reduced need for pain medication during labor, and lower likelihood of having a caesarean delivery or instrumental vaginal birth. Continuous support was also associated with lower rates of depression and improved Apgar scores of the newborn .The evidence that birth companionship improves labor outcomes and experience of care has been available for many years. As such, global guidance supports birth companions. The World Health Organization (WHO) states “continuous companionship during labor and childbirth is recommended for improving women’s satisfaction with services;”  and a coA 2019 Cochrane review outlined common barriers to facilities adopting birth companionship: health facility policies, provider attitudes, facility infrastructure, and preparation of families and birth companions . ImplemeThis study will evaluate an intervention package of eight elements to increase birth companion coverage based on the framework described in the Cochrane review Fig.  24]. It. It24]. Orient facilities and providers to benefits of birth companionship. Key individuals  from each intervention facility will be oriented on the benefits of birth companions. We will arrange for a benchmark visit to a facility where birth companions have been incorporated into practice, where possible.Develop/update formal standard operating procedures (SOPs) for implementing birth companions and plan to implement guideline/SOP. We will develop a template to be provided to each intervention facility along with an existing SOP that can serve as an example. We will identify individuals in these facilities to participate in the development of a SOP and one person to lead the process. A workshop will be conducted to develop the SOP. Participants will include staff, postpartum women with experience of having a birth companions, and birth companions. The SOP will be finalized and endorsed by the facility director or designee.Design and complete rapid physical space and assess data needs for audit and feedback cycles. We will develop a template, which, together with the intervention facility staff, will be used to assess and determine the physical/environmental changes or enhancements that are needed to incorporate or increase use of birth companions . We will then support the facilities to make the necessary changes and procure the required equipment and supplies. We will initially assist facilities to assess their data availability to measure coverage of birth companions as part of facilitating audit and feedback cycles. If additional data is required, we will work with the facility to develop methods to measure coverage and then establish targets.Develop resources on how to support women and a means to distinguish/recognize the birth companion. We will assess the available birth companion-related resources and either adapt or develop new materials . Job aids for care providers will allow them to communicate the benefits of birth companions to pregnant women and clarify the role of providers and birth companions. For mothers, the resources will promote the presence and importance of birth companions. For birth companions, the materials will explain their role during labor, birth, and the postnatal period. We will also assess the best way to designate the birth companions  and provide the facilities with the necessary materials.Prepare providers to integrate birth companions into the care team. An orientation and planning meeting will be conducted to operationalize the SOP with intervention facility staff working in antenatal care (ANC) clinic and labor and delivery ward (including support staff). Community health workers will also be included so they can raise awareness about the birth companion intervention.Orient ANC clients to rationale for and selection of a birth companion. After the launch of the intervention, pregnant women anticipating delivery in intervention facilities will be oriented to birth companions during ANC, optimally during their third trimester ANC visit. Similar information will also be available in the labor ward, ensuring that the information reaches women who did not have a third trimester ANC visit at intervention facilities. Pregnant women who are close to their due date will also be reminded by community health workers in the intervention health facilities’ catchment area to plan on having a birth companion. We will use developed materials to communicate the benefits of birth companion.Prepare birth companions to support women. Birth companions in intervention facilities will be oriented using the resources developed  on their role and how they can best support the woman during labor, birth, and the postnatal period. We will also ensure that birth companions are easily recognizable .Begin audit and feedback cycle to iterate model and track intervention. We will support existing facility meetings to review data. Facilities will modify implementation of the package, as needed, to increase coverage. We will capture modifications to the intervention through process documentation.Use of a birth companion will be voluntary for participants and non-participants who seek care at study site facilities. There are no retention strategies for women or companions for the intervention. Staff at intervention facilities will be supported to implement the package through on-site monitoring and audit and feedback cycle data reviews.To determine the feasibility and acceptability of the birth companion intervention package to increase coverage of birth companions during labor, birth, and the postnatal periods.This study will use a two parallel arm cluster randomized controlled trial (cRCT) design stratified by country/county and birth volume, with 12 public health facilities in Ethiopia, 24 public health facilities in Kenya, and 24 public health facilities in Nigeria. This study will be happening in and near Addis Ababa city of Ethiopia, Machakos and Murang’a counties of Kenya, and Kano and Nasarawa states of Nigeria Tables .We will use a mixed methods approach to assess impact of the birth companion intervention package and measure the study outcomes with exit interviews, health facility register data extraction, in-depth interviews (IDIs), focus group discussions (FGDs), and key informant interviews (KIIs).There are five data collection periods. We will first conduct a baseline assessment over the course of approximately four weeks, in facilities meeting the inclusion criteria. Health facilities that decline to participate in the study will be replaced by another facility. Facilities will be randomized after the baseline survey in a 3:1 ratio . Randomization is stratified by the number of facility deliveries and by country (Ethiopia) or by county or state within a country (Kenya and Nigeria). Intervention facilities will prepare to introduce the birth companion intervention package over the course of approximately two months to facilitate the presence of birth companions during labor, birth, and the postnatal period. Control facilities will continue to provide the local standard of routine care which may or may not include a birth companion. Facilities will not be replaced or reallocated to study arm post-randomization. This study does not place restrictions on facilities or participants regarding participation in other interventions or research.We will have three quarterly quantitative and qualitative data collection periods, each lasting for approximately one week. We will conduct an endline quantitative survey, approximately 12 months after birth companion intervention initiation. Mothers, birth companions, health care providers, and unit managers in study facilities will have the option to decline to participate in the study.At the end of the study, control facilities will be supported to implement the birth companion intervention package by staff from an intervention facility that has a birth companion coverage of approximately 50% or higher see Fig. , assuminThe study population will include: eligible women who give birth at participating facilities; birth companions of eligible women; all eligible providers working in the ANC, and labor, birth, and postpartum wards; and unit managers who work in the facilities during the study period. Inclusion and exclusion criteria are shown in Table The sample size justification is based on estimating coverage of birth companionship. We assumed a within-facility intra-class correlation coefficient (ICC) between 0.05 and 0.5 (higher is more reasonable). We also assumed post-birth companion support coverage at 50%. Baseline/standard practice birth companion coverage varied between 5% and 20%.Sample size is calculated separately by country for two-sample comparison of proportions (with pooled Z-test) in a cluster randomized design using PASS . NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass) .The calculations below apply to the study area in Ethiopia, the two study counties in Kenya, and the two study states in Nigeria. We assume the same baseline level of birth companion coverage in all three countries. There are the same total number of facilities to be randomized at each study area, n = 12 (three in the standard arm and nine in the intervention arm). There will be a total of 12 facilities in Ethiopia, 24 in Kenya, and 24 in Nigeria.The number of women per facility and total number of women across the two study arms per study site needed was calculated for at least 80% statistical power to test differences in proportions of birth companion coverage between study arms at 0.05 level of statistical significance, assuming that for every three facilities randomized to the birth companion intervention, one facility will be randomized to the standard practice arm and a coefficient of variation of one. Post-birth companion intervention coverage is assumed to be 50%.Conservatively assuming 20% birth companion coverage in the standard practice (control) arm and 50% in the birth companion intervention arm at the endline, to have 80% statistical power to detect this difference in proportions at 0.05 level of statistical significance, coefficient of variation of one, we will need to include 62 women who recently gave birth (on average) at each of the 12 health facilities per study area, for a total of approximately 744 women across the two study arms . In this scenario in each of the study sites , three facilities will be randomized to the standard arm, and nine facilities to the birth companion intervention arm. Since the coefficient of variation is almost one, based on the facility data presented in Tables For mothers in intervention facilities, we will include both women who reported having and not having a positive experience with their labor and birth care from the quantitative survey. We will assess the acceptability of birth companions by interviewing mothers who had a birth companion in intervention facilities. We will also interview their birth companions, including husbands/partner, other family members, and friends. For providers and unit managers, we will select some staff from intervention facilities where birth companion coverage is high and some from where birth companion coverage was low. We will plan to have up to approximately 16 interviews with mothers and birth companions. We will also have approximately eight FGDs with providers and eight KIIs with unit managers Table .Proportion of women at study facilities that have a birth companion during labor, birth, and the postnatal period.Experience of careAmong those who report having a birth companion, proportion who report that the birth companion was the one of their choice.Mothers’ perception of the birth companion experience.Mothers’ score on Person-Centered Maternity Care scale , compari4.Proportion of providers and unit managers who report the physical environment of care supports the presence of birth companion during labor, birth, and the postnatal period.5.Mothers’, birth companions’, providers’, and unit managers’ perception of birth companions.6.Score on facility readiness to change.7.Facility-level costs for updates to physical environment of care and other implementation costs.Data will be collected at baseline and approximately quarterly for approximately one year after the birth companion intervention package implementation is introduced in all study facilities. Qualitative data will be collected approximately quarterly at intervention facilities. The recruitment process by study participant type is detailed in Table Privacy will be ensured by offering study participation (recruitment) in a space in the facility or outside the facility that allows for audio and visual privacy. We do not expect participation in this study to be associated with any mentioned risks.Study staff will have a minimum of secondary and post-secondary training. They will be trained on basic research ethics and the study procedures. The Johns Hopkins School of Public Health (JHSPH) Ethics Field Training Guide will be used during the training.For all study participants, the information that will be collected by this study team will be kept confidential. The information will not be accessed by anyone except the study team, and it will only be used for this research purpose. No individual identities will be used in any reports or publications resulting from the study. Procedures for consenting study participants are described below.A data collector will be placed at each facility during the data collection periods. Consent documents will be translated into the local languages. If possible, the data collectors will approach women when they arrive at the facility and screen them to assess their eligibility . Informed consent will be obtained after the birth in a private space within the facility. For the qualitative study, women who consent to participate in the study will be asked if they had a birth companion. If present, a similar procedure will be followed for consenting birth companions. In the consent process, potential participants will be informed of why they were chosen, their rights as participants, risks, and benefits. Anyone declining consent will not be included in the study. Surveys and interviews will be administered after consenting the clients. Confidentiality will be kept to the maximum standard during data collection and data handling.Providers and unit managers in ANC, labor and birth wards of intervention facilities will be approached for consent for the duration of the study (approximately 16 months) by study staff. Providers and unit managers will be oriented on the study, informed of why they were chosen, their rights as participants, risks, and benefits. Anyone declining consent will not be included in the study. New providers and unit managers will be consented at the time of data collection. All surveys, interviews and IDIs will be administered after consenting the clients. During the baseline survey, providers will be asked to respond to the facility readiness to change survey. For IDIs and FGDs, they will be approached quarterly after the launch of the intervention. For the quantitative feasibility study, providers in the intervention facilities will be approached during the endline survey. Every effort will be made to protect the confidentiality of participants, but due to practical constraints , it may not be possible to guarantee that supervisors will remain unaware of participation.Pre- and quarterly post-intervention data will be collected from facilities. All women who deliver in the intervention and control facilities during the data collection period and meet the eligibility criteria will be interviewed prior to being discharged. Basic demographic data  will be collected. Structured questionnaires will be used to assess coverage of birth companion, choice of birth companion (if present) and experience of care. The person-centered maternity score has been validated and is a 30-item scale . It has To explore the experience of having a birth companion, we will conduct quarterly interviews with mothers in intervention facilities who meet the inclusion criteria. Acceptability of the birth companion intervention will also be assessed quarterly by conducting IDIs with both women who had a birth companion and their birth companions in intervention facilities. Specific topics to be explored with mothers include: their awareness of the birth companion concept; support/advice they received about having a birth companion; their choice and reason for choosing the birth companion; the type of support their birth companion provided; and their experience of/satisfaction with the care from providers in the presence of birth companion. The following domains will be explored with birth companions including their experience of being a birth companion; how they provided support to mother; their self-reported preparedness to be a birth companion; their perceptions of the orientation materials ; and the means used to designate them as a birth companion.To assess the acceptability as well as feasibility of the birth companion intervention from the supply side, we will conduct FGDs with providers in labor and birth wards and KIIs with unit managers who meet the eligibility criteria. FGDs with providers at intervention facilities will include: their experience of being oriented on the birth companion concept; the materials provided for supporting the birth companion intervention; the physical and managerial level support of the birth companion intervention; and, their experience of and attitudes towards having a birth companion during labor, birth and the postnatal period; perceived changes in their communication and relationship with clients (if any); changes in their workloads; sustainability of having birth companions; and, suggested changes to the model required to offer birth companions. KIIs will be conducted with unit managers in intervention facilities to explore the processes, and where present, challenges of developing birth companion SOP; care provider’s orientation; facility adjustments to facilitate birth companions; integrating birth companions into the care provided; and monitoring the birth companion coverage.The following methods will be used to describe group characteristics or differences: for categorical variables, the number, and percent in each category; for continuous variables, the mean, median, standard deviation, quartiles, and range . Adequacy of the randomization will be assessed at baseline by comparing characteristics of participants and facilities in intervention and control arms, including demographics, birth companion coverage, and experience of care.Proportion of mothers whose births included birth companions will be reported and compared between intervention and standard care arms at the end of the intervention using cluster-weighted chi-square test , 27. If The model will include birth companion status at birth as the study outcome, study arm as the primary predictor, and adjustment for covariates that are differentially distributed between the study arms. The primary analysis will be conducted separately for each sub-national region.For the binary secondary quantitative outcomes, we will use similar analytical methods as for the primary outcome. For continuous outcomes, such as facility readiness for change or score on the Person-Centered Maternity Care scale, we will use a cluster-weighted t-test. As in the case of the primary outcome, linear regression models with cluster-correlated standard error estimates will be used to compare the study arms while adjusting for covariates that are differentially distributed between the study arms.If the proportion of missing data on these covariates is more than 5%, we will use statistical imputation for missing data. Similarly, if the proportion of missing outcome data is small (< 5%), then complete-case analyses will be used. If the amount of missing data for the study outcomes is > 5% or if it is suspected that missingness for the outcome data are not completely at random, based on examination of reasons for missingness, a series of sensitivity analyses for the distribution of missing outcome data will be performed.Audio recordings of interviews and FGDs will be transcribed from the local language to English by individuals proficient in the local language and English. The transcriptions will be spot checked for quality against the recordings by study staff conversant in both English and local languages used. Thematic analysis will be employed. As qualitative research is a learning experience in the field, emerging themes in the field shall be considered for inclusion in subsequent data collection activities after discussion by senior research management at Addis Continental Institute of Public Health (ACIPH), International Center for Reproductive Health Kenya (ICRHK), and Maternal and Reproductive Health Research Collective (MRHRC). Analysis will be on-going. Coding of textual passages will be done in Atlas-ti or other qualitative data analysis software. Qualitative data analysts will have training and experience in coding of textual information on health topics. The emerging themes will be summarized in tables and other appropriate formats.Data collectors will receive in-depth training on the study objectives, procedures, and ethics by ACIPH, ICRHK, and MRHRC. A detailed manual with SOPs will be prepared and used in training, piloting, and research. The training will also include proper use of tablets and SurveyCTO, which will be used for data entry at the point of collection. There will be daily checks for completeness and consistency of the collected data. The electronic data capturing system will limit data inaccuracies by building in logic, range, and skip-patterns, and minimizing outliers. Investigators will also be supported with ongoing supervision visits from ACIPH, ICRHK and MRHRC.Data will be de-identified after data collection by ACIPH, ICRHK, and MRHRC and shared with John Hopkins Biostatistics Center for multi-country analysis. De-identified data will be archived according to Bill & Melinda Gates Foundation policies on Synapse or a similar platform. We will also adhere to ACIPH, ICRHK and MRHRC data sharing policies.ACIPH, ICRHK and MRHRC will also provide training on study objectives, step-by-step training procedures and guidelines of data collection, recording, and transcribing recordings, and ethics of data collection. Audio recordings of interviews and FGDs will be randomly selected and compared against transcripts for data quality monitoring.No data or safety monitoring oversight is planned for this study. External audits will occur if requested by local regulatory entities. Data security will be carefully and continuously maintained, with limited secure access to data. All study data collection and administrative forms will be identified by coded number to maintain participant confidentiality. All records that contain names or other personal identifiers, such as locator forms and consent forms, will be stored securely. All local databases will be secured with password protected access systems. To the extent possible, we will minimize risks to confidentiality during data collection by directly entering data into the secure database without the use of paper forms. Participant confidentiality will be ensured during FGDs and KIIs by conducting interviews in a secure location, preferably a closed-door room in a health facility, or, in the case of KIIs, within the participants’ offices.Quarterly study findings will be shared with health care providers. The final study results will be published as scientific articles and reports. No professional writers will be used. Publications arising from this evaluation will follow the recommendations from the International Committee of Medical Journal Editors.We do not anticipate that this study will result in adverse events. If any unanticipated adverse event or problems occur, the PI will report such occurrences to the JHSPH Institutional Review Board (IRB) and to the local IRBs in Ethiopia, Kenya, and Nigeria, with all reporting and response according to IRB policies and recommendations.This protocol describes the birth companion intervention and the research in Ethiopia, Kenya, and Nigeria. Despite strong evidence and global recommendation in support of birth companions, many women continue to give birth alone in unfamiliar, and often poor quality, facility settings. This study of a low-cost intervention package will provide important evidence for overcoming common barriers within hospitals and health centers that currently discourage or prevent women from having a birth companion.This trial is registered with ClinicalTrials.gov with identifier: NCT05565196, first posted October 4, 2022. This trial is currently recruiting. Baseline surveys were conducted in Ethiopia October 10─November 22, 2022 and in Kenya from November 1─December 9, 2022. For Nigeria, we have received ethical clearance and are preparing to conduct the baseline survey. We anticipate reaching study completion in mid- to late-2024.Version 1.6, September 2023.


The purpose of the study was to determine the possible relationship between the eruption of primary and permanent teeth and neonatal factors in German children according to gender.A cross-sectional survey study was performed in 10 German orthodontic practices. Using a questionnaire information about gender, time of birth (week of pregnancy), birth weight (g) and height (cm), and the age of first primary and first permanent tooth eruption (months/years) of 405 children (230 girls and 175 boys) were collected. A Mann–Whitney U-test was used for group comparisons, and correlations were verified using a Pearson test.No correlation was found between neonatal factors  and primary tooth eruption for male participants. However, for females a low correlation was found between the eruption of the first primary tooth and birth weight  and birth height . No correlations between neonatal factors and the eruption of the first permanent tooth were found for either gender. A moderate correlation was found between the first primary and first permanent tooth eruption .An earlier eruption of the primary teeth can be assumed with greater body weight and height at the time of birth for girls. For boys, the tendency is the opposite. However, there seems to be a catch-up growth effect due to the missing differences between both permanent tooth eruption times. Nevertheless, the first primary and the first permanent tooth eruption correlates in a German children population. The timing and sequence of tooth eruption are important factors in orthodontic treatment planning and forensic dentistry to predict the age of a child. Tooth eruption is a continuous biological process in which a growing tooth erupts from the jaw through covered mucosa into the oral cavity and the fossa of the opposing tooth . DiffereIt has generally been found that girls usually get their permanent teeth earlier than boys , 9. The Regarding the time of birth (week of pregnancy), the incidence of preterm birth varies from 5 to 13% in developed countries –14. In tRegarding height and weight, Kutesa et al. found a moderate correlation between these body characteristics and the dentition development of a population group in Uganda . SimilarOnly a few studies investigated the possible relationship between the tooth eruption of primary dentition and permanent dentition. In a cohort study, Poureslami et al. were able to confirm a significant correlation with regard to the eruption times of both kinds of teeth, but it was independent of socioeconomic status . They shThe purpose of the present study is to investigate the possible relationship between primary and permanent tooth eruption, gender and neonatal factors in German children. It should be determined whether there is a systematic correlation between birth week, birth weight and birth height and the first primary or first permanent tooth eruption. Furthermore, it will be analyzed if there is a possible correlation between the beginning of the eruption of the deciduous and permanent dentition.This cross-sectional study was performed in 10 randomly selected orthodontic practices in North Rhine-Westphalia, the most populous state in Germany, and Lower Saxony, the second largest state in Germany. The investigation was conducted between April and December 2016 as a survey. The ethical guidelines of the Helsinki Declaration and its later revisions were followed in all procedures carried out in this study, and ethical approval was given by the ethics committee of the University of Witten/Herdecke (189/2015).The initial presentation to the orthodontic practices was made on the parents/guardians’ initiative or due consultative referral. An orthodontic treatment need was not a requirement for inclusion in the study. The children were selected according to Poureslami et al.  considerPrior to the questioning, written consent was received from the parents/guardians on behalf of the children, and the children’s assent was obtained after participation was explained by a specially instructed member of each practice. The exclusion criteria were children with clefts or syndromes, agenesis or early tooth loss caused by caries or traumatic events and hormonal disturbances. The survey was carried out using a specially developed questionnaire, which the parents/guardians filled out. Participation in this survey was only agreed upon by the examiners if the parents/guardian were absolutely certain about the correctness of the provided information. The questionnaire included questions about:Date of birth and genderTime of birth (week of pregnancy)Birth weight (g) and height (cm)Age at the first primary tooth eruption (in months) and first permanent tooth eruption (in years).P ≤ 0.05 by using the statistical program Prism . All results are expressed as mean ± standard deviation values, as well as minimum, median and maximum.The a priori sample size calculation was performed using the G Power software  with the Wilcocon-Mann-Whitney test for mean differences between groups. Considering the data of Poureslami et al.  about thP-values of the statistical comparisons between the genders for the neonatal factors and the eruption times of both dentitions based on a Mann–Whitney U test. Table Table After completing the data collection, it was possible to access data sets from a total of 405 children—230 girls (56.5%) and 175 boys (43%). In some cases, the questionnaire was not completed in full  for male patients. However, for females a low correlation was found between the first primary tooth eruption and birth weight  and birth height . No correlations between neonatal factors and the first permanent tooth eruption was found for female or male patients. However, a slight to moderate correlation was observed between the first primary and first permanent tooth eruption .The overall aim of the present study was to investigate the existence and extent of systematic correlations between first tooth eruption in primary dentition and permanent dentition and whether these are possibly influenced by neonatal factors . To that end, a survey study was conducted from April to December 2016 in 10 orthodontic practices in North Rhine-Westphalia and Lower Saxony, Germany.There are some points in the study design that must be considered as critical and limited with regard to the interpretation of the present results and its associated meaning of significance. Concerning the participant selection, it must be noted that other potential factors, such as genetic, nutritional or hormonal factors, were not taken into account or excluded, which must be considered as drawback due their effect have already described . The samThe significance of birth week and birth size in relation to the timing of the first deciduous tooth eruption has been debated in the literature. Based on international comparisons, regional differences seem to exist. In this context, Soliman et al.’s study of 1132 Egyptian children  showed that boys seem to be ahead of girls with regard to the number of erupted teeth in relation to birth weight and height . In a loIn the present investigation, no significant correlation between birth week and age at first primary tooth eruption was detectable. However, regarding birth weight and age at eruption of the first deciduous tooth, a significant correlation was found for the female participants. The higher the birth weight of the girls, the younger they were at the first primary tooth eruption. The opposite trend was observed in boys; the higher the birth weight, the older the male participants were when the first deciduous tooth erupted. However, for boys this was not confirmed statistically. The analysis of the present data to determine a correlation between birth height and age at first primary tooth eruption also showed a significant correlation for the female participants. Similarly, the effects were opposite in boys and girls, although they were not statistically significant for the male participants. This means that for girls, the larger they were at birth, the younger they were at the eruption of the first deciduous tooth and for boys, the larger they were at birth, the later the first primary tooth erupted.Therefore, our results confirm those studies that do not describe a correlation between birth week and the first primary tooth eruption but show that there seems to be gender-specific correlations with regard to birth size or weight. This suggests that, compared to boys, girls who are comparatively heavier and taller at birth may have earlier eruption of deciduous teeth.Concerning gender, there is agreement in the literature that girls’ permanent teeth erupt earlier than boys’ permanent teeth –27. In gIn contrast to these findings, in the present study no significant correlation between week of birth, birth weight or height and the age at first permanent tooth eruption was found, either in the overall collective or in girls or boys. Therefore, previous interdependencies concerning the second dentition cannot be confirmed.Associations have been reported between maturity of primary dentition and permanent dentition showing that a small number of primary teeth at 1 year of chronological age is related to less mature permanent teeth at an age between 9 and 11 years in preterm children . PoureslNo systematic correlation between the week of birth and the time of the first primary or first permanent tooth eruption was found. However, it is determined for girls that with increasing body weight and size at the time of birth, an earlier eruption of the primary teeth has to be assumed. For boys, the tendency is the opposite. Regarding the second dentition, there is no such correlation. This is probably due to the catch-up growth effect, which has already been discussed in the literature. But there is a systematic, statistically significant correlation between first primary tooth eruption and first permanent tooth eruption. However, the present findings are limited and must be critical considered with regard to the low statistical significance, which is attributed to the small sample size, as well as the underlying low validity, which based on the character of the present participant survey. This is attributed to the small sample size and the participant related reliability about the retrospective collected measurements. In order to improve this, prospective epidemiological research like monitoring studies will be necessary, which could then also analyse the entire dentition.


It remained unclear whether isolated positive thyroid peroxidative antibodies (TPOAb) were associated with adverse maternal and neonatal outcomes. The purpose of this study was to observe adverse neonatal outcomes among euthyroid pregnant women with positive TPOAb and to investigate the underlying risk factors.Euthyroid pregnant women with TPOAb positivity were enrolled and followed up in our study. Adverse neonatal outcomes such as preterm birth, low birth weight, and fetal macrosomia were observed. Clinical data in the first trimester were collected and compared between groups with or without adverse neonatal outcomes. Maternal serum soluble CD40 ligand (sCD40L) was also measured at the same time.P < 0.05). Multivariate regression analysis showed that sCD40L and receiving ART were the independent risk factors for adverse neonatal outcomes. The odds ratio values of sCD40L higher than 5.625 ng/ml were 2.386  for overall adverse neonatal outcome, 3.900  for preterm birth, and 3.149  for low birth weight.A total of 176 euthyroid pregnant women with TPOAb positivity were finally enrolled and analyzed in our study. Thirty-nine (22.16%) euthyroid women with TPOAb positivity were found to have adverse neonatal outcomes. Thirteen participants received assisted reproductive technology (ART) in our study, and seven participants were in the adverse neonatal outcome group. Preterm birth, low birth weight, and fetal macrosomia were the most common comorbidities. The proportion of receiving ART and the levels of sCD40L and platelet were significantly higher in the adverse neonatal outcome group (all Approximately one of the four euthyroid women with TPOAb positivity might have adverse neonatal outcomes. Measurement of sCD40L in first trimester might have a predictive value for adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb. Thyroid hormones are important determinants for the development of fetuses, especially in early pregnancy . ThyroidIsolated positive TPOAb women are particular phenotype that is defined as having normal thyroid function and positive TPOAb in circulation. Studies have shown that euthyroid women with TPOAb positivity were also associated with preterm birth, abnormal fetal growth, and so on –7. It wain vivo. Soluble CD40L (sCD40L) is produced by the shedding of CD40L and has similar functions to CD40L  and normal thyroid-stimulating hormones (TSH) in serum.The 2017 American Thyroid Association (ATA) guideline advocates the use of population-based reference ranges of TSH during pregnancy, whereas if these ranges are not available, they recommended using 4.0 mIU/L as the upper reference limit of TSH for the first trimester. Thus, TSH values > 4 µIU/ml were excluded in our study to eliminate the possible effect of subtle thyroid dysfunction .All participants enrolled in the first trimester and follow-up until childbirth. Inform consent was signed in each participant before the enrollment. Adverse neonatal outcomes  were recorded and analyzed.Premature birth was defined with newborns whose gestational age is less than 37 weeks but more than 28 weeks. Low birth weight was defined with newborns whose birth weight is less than 2,500 g. Fetal macrosomia was defined with a newborn with a birth weight of more than 4,000 g. The flow diagram of study was summarized in The exclusion criteria for the participation in the study are as follows: age > 45 years old, missing data/records during follow-up, previous history of thyroid disease, previous history of diabetes mellitus or gestational diabetes mellitus , medicatThe demographical data of all participants such as age, gestational weeks, gravida, parity, pre-pregnancy body mass index (BMI), receiving assisted reproductive technology (ART) or not, type of ART such as in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI) were recorded in the early pregnancy. All participants will undergo a routine obstetric examination in our hospital. Data of glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), ferritin, uric acid (UA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c), C-reactive protein (CRP), white blood cell (WBC), red blood cell (RBC), hemoglobin (Hb), and platelet were also collected.Serum levels of TSH, FT4, and TPOAb of all participants in gestational weeks 10–13 were measured. Serum levels of TSH, FT4, and TPOAb were measured using automated chemiluminescent immunoassays . Reference ranges used in our study were as follows: TSH, 0.35~4.94 μIU/ml; FT4, 9.01~19.04 pmol/L; TPOAb, <12 IU/ml.Fasting blood was collected in all participants in the early stage of pregnancy. Serum sample was store in −80°C refrigerator for centralized measurement. A commercial ELISA kit  was used to measure serum sCD40L. The minimum detectable dose was 0.015 ng/ml, with intra- and inter-coefficients of variation of <5%.P-value of 0.05 or less was considered statistically significant.Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 8.0.2. The data were tested for normality using the Kolmogorov–Smirnov test. Data are presented as mean ± standard deviation for normally distributed variables or median (5% and 95% interquartiles) for nonnormally distributed variables. According to the adverse neonatal outcomes, the participants were divided into two subgroups. The differences between groups were compared by Student’s t-test or Mann–Whitney U-test. The Fisher’s exact test was used to test categorical variables. According to types of adverse outcomes, participants were divided into four subgroups. The differences among subgroups were performed with nonparametric test. Logistic regression analysis was carried out to evaluate the odds ratio (ORs) and 95% confidence interval (95% CI) of adverse neonatal outcome in euthyroid pregnant women with positive TPOAb. P = 0.012, P = 0.265, A total of 176 euthyroid pregnant women with positive TPOAb with complete data were finally enrolled and analyzed in our study. Thirty-nine of the 176 (22.16%) participants were having adverse neonatal outcomes. According to the occurrence of adverse neonatal outcomes, the participants were divided into groups: with adverse neonatal outcome (n = 39) and without adverse neonatal outcome (n = 137). The baseline and laboratory characteristics of the patients were provided in P < 0.001, P = 0.005). A positive correlation was found between sCD40L and platelet . There was no correlation between sCD40L and other parameters.Platelet and sCD40L were significantly higher in participants with the adverse neonatal outcome group  participants had adverse neonatal outcome including preterm birth , low birth weight , and fetal macrosomia .P = 0.005, P = 0.019, and P = 0.047; sCD40L levels of participants were 8.28 ± 4.15 ng/ml in the overall adverse neonatal outcome group, 8.60 ± 4.14 ng/ml in the preterm birth group, and 8.49 ± 4.65 ng/ml in the low birth weight group. sCD40L levels were found to be significantly higher in overall adverse outcomes, preterm birth, and low birth weight .Platelet counts were also found to be significantly higher in overall adverse outcomes, preterm birth, and low birth weight (9/L with an average AUC 0.647 (95% CI = 0.547 to 0.746), respectively.Receiver operator characteristic (ROC) curve analysis was performed for the diagnostic performance of sCD40L and platelet levels for overall adverse neonatal outcomes Figure 3P = 0.046; and OR = 7.384, 95% CI = 1.704 to 31.995, P = 0.008; As we unexpectedly found that sCD40L, platelet counts, and the proportion of ART received were significantly higher in the group with adverse neonatal outcome, we attempted to evaluate the association of these risk factors with adverse neonatal outcome in euthyroid women with positive TPOAb. Our results revealed that serum sCD40L levels higher than 5.625 ng/ml and receiving ART were the independent risk factors for overall adverse outcome in euthyroid pregnant women with positive TPOAb in the first trimester  euthyroid pregnant women with positive TPOAb had adverse neonatal outcomes during pregnancy. Preterm birth, low birth weight, and fetal macrosomia are the most common comorbidities. We found that serum sCD40L was significantly higher in the group with adverse neonatal outcome. Logistic regression analysis showed that sCD40L > 5.625 ng/ml in early pregnancy was independent risk factor for overall adverse neonatal outcome group and preterm birth. We proposed that the measurement of sCD40L in early pregnancy might have predictive value for adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb.Maternal thyroid hormones are dispensable for the development of the fetus, especially before the 20th gestational week, because the thyroid gland in the fetus is not well developed , 2. It iThere are several possible explanations for the association of isolated TPOAb positivity with adverse pregnancy outcomes. Relative insufficiency of thyroid hormones due to positive TPOAb and the presence of thyroid antibodies and potential autoimmune disorders were possible underlying mechanisms of TAI-related adverse pregnancy outcomes . Women wCD40-CD40L is a pair of membrane molecules. Both belong to the tumor necrosis factor receptor family and play an important role in the immune inflammatory response , 13. sCDA total of 13 (7.3%) participants received ART in our study. Receiving ART was closely linked to the adverse neonatal outcome such as preterm birth and low birth weight in our study, which was consistent with previous report , 19, 33.Another interesting finding was that TSH was a risk factor for low birth weight in isolated positive TPOAb women in our study (as shown in The strengths of our study were as follows. First, all participants enrolled and analyzed in our study were euthyroid according to 2017 ATA guidelines. Thus, the possible effect of thyroid dysfunction was eliminated. Second, we concentrated on the adverse outcomes of euthyroid pregnant women positive for TPOAb and found, for the first time, that costimulatory molecules had a predictive role for adverse outcomes in early pregnancy.This study also has some limitations. First, the sample size for this longitudinal observational study was small. Larger cohort studies are needed for further investigation, and sCD40L throughout pregnancy needs to be investigated. Second, we did not have longitudinal data on thyroid hormones before and after pregnancy. Furthermore, the predictive value of the marker should be further validated in clinic.In our study, we found that one of the four euthyroid women with TPOAb positivity might have adverse neonatal outcomes during pregnancy. These patients need to be carefully monitored during pregnancy. Increased sCD40L levels in the first trimester might be potential biomarker for adverse neonatal outcomes in pregnant women positive for TPOAb.The clinical data of the population used to support the findings of this study are available from the corresponding author upon request.This study was approved by the Institutional Review Board of Suzhou Municipal Hospital affiliated to Nanjing Medical University. The patients/participants provided their written informed consent to participate in this study.XXC and QW proposed and designed the study and performed the statistical analysis work. HZ, QS and XGC collected data and followed up the participants. XXC drafted the manuscript. LC reviewed and edited the manuscript and funding acquisition. All authors contributed to the article and approved the submitted version.


To identify the factors associated with Baker’s cyst rupture on MRI.From January 2021 to December 2022, a total of 441 knee MRI examinations in 441 patients (mean age: 47.7 ± 13.8 years) with Baker’s cyst were included in this study. Patients were classified into two groups: those with ruptured vs. unruptured Baker’s cysts. On knee radiograph, osteoarthritis grade was assessed based on Kellgren-Lawrence grade. On MRI, combined structure injuries, alignment type between semimembranosus tendon and medial head of gastrocnemius tendon, amount of joint effusion, presence of septation, maximal diameters of cyst, and cyst volume were evaluated. Receiver operating characteristic (ROC) analysis was performed to assess the predictive performances of imaging factors for cyst rupture.p = 0.035) and larger volume  than those without rupture. On ROC analysis, maximal transverse diameter of cyst ≥ 22.2 mm  and cyst volume ≥ 10.9 cm3  were the cutoff values for predicting rupture of cyst, respectively. The cyst volume showed significantly higher area under the curve (AUC) than maximal transverse diameter .There were 146 patients with Baker’s cyst rupture and 295 patients without rupture. Patients with cyst rupture showed significantly longer maximal transverse diameter (25.8 ± 6.8 mm vs. 21.6 ± 5.8 mm, Longer transverse diameter and larger volume of Baker’s cyst could be predictive imaging parameters for cyst rupture. Baker’s cyst is a fluid collection in the medial gastrocnemius-semimembranosus recess between the semimembranosus tendon (SMT) and medial head of gastrocnemius tendon (MHGT) . Baker’s1235Previous studies reported that Baker’s cysts were associated with some kinds of intra-articular disorders such as chondral lesion, degenerative osteoarthritis (OA), rheumatoid arthritis, meniscal tear, and anterior cruciate ligament (ACL) tear 57. Howev57MRI is the gold standard of diagnosing Baker’s cyst . TherefoThis retrospective study was approved by our Institutional Review Board, and the requirement for informed consent was waived.From January 2021 to December 2022, all knee MRI examinations taken at our institution due to the knee pain were eligible for the inclusion in this study. Among them, a total of 441 knee MRI examinations in 441 patients with Baker’s cyst was included in this study. Most of the patients  underwent unilateral knee MRI, and the remaining 46 patients (10.4%) underwent bilateral knee MRIs, but Baker’s cyst was present on only one side. Subjects were divided into two groups: ruptured vs. unruptured Baker’s cyst. Ruptured Baker’s cyst was defined when there was ill-defined high signal intensity on T2-weighted image in the adjacent soft tissue along the cyst . The eleMRI was performed by 3.0-T  MR scanners with the unenhanced knee protocol. The standard protocol consisted of axial T2-weighted fat saturation (FS) , coronal T1-weighted  and T2-weighted FS , and sagittal proton density-weighted  and T2-weighted FS  sequences with a 23-channel body coil. The field of view (FOV) and acquisition matrix was 18 × 18 cm and 384 × 288, respectively.Two radiologists  independently reviewed all images. When there were discordant results, consensus was reached with another radiologist (eleven years of radiology experience).ap × rt × rh (The OA grade was assessed on anteroposterior (AP) radiographs of knee joint obtained at the same day of the MRI examination based on Kellgren-Lawrence (K-L) grade . Then, t rt × rh .t-tests, and categorical values were compared using Pearson’s chi-square or Fisher exact tests. Inter-reader agreements for categorical values were assessed by kappa (κ) statistics and those for continuous values were assessed by intraclass correlation coefficient (ICC). Kappa values were interpreted as follows: less than 0.20, poor; 0.21–0.40, fair; 0.41–0.60, moderate; 0.61–0.80, good; and greater than 0.81, excellent agreement. ICC results were interpreted as follows: less than 0.50, poor; 0.50–0.75, moderate; 0.76–0.90, good; and greater than 0.90, excellent [P value < 0.05 was considered statistically significant.Statistical analyses were performed by IBM SPSS Statistics for Windows, version 27.0 . Continuous values were compared using independent sample xcellent 12. The pxcellent . P valuep = 0.035) and larger volume  than those without rupture. There was no significant difference in other factors (Among 441 patients with Baker’s cysts (mean age: 47.7 ± 13.8 years), 146 patients had a ruptured Baker’s cyst, while 295 patients showed no signs of rupture. Patients with cyst rupture showed significantly longer maximal T diameter  (p = 0.002).On ROC analysis, maximal T diameter of cyst ≥ 22.2 mm was determined as the cutoff value for considering rupture of Baker’s cyst with 64.4% sensitivity and 54.9% specificity . Furthermore, cyst volume ≥ 10.9 cm4–0.778) . The cysp = 0.035) and larger cyst volume  than those without cyst rupture. Furthermore, maximal T diameter of cyst ≥ 22.2 mm and cyst volume ≥ 10.9 cm3 were the cutoff values for predicting rupture of cyst, respectively. The cyst volume showed significantly higher AUC than maximal T diameter.In our study, patients with Baker’s cyst rupture showed significantly longer maximal T diameter  were excluded. Though, in patients with Baker’s cyst rupture, only ill-defined T2 high signal intensity without visible cyst after total shrinkage of cyst can be seen on MRI; it is often hard to differentiate MRI findings of cyst rupture from other diseases, such as tenosynovitis, bursitis, muscle strain, etc. This can affect the result of our study. Third, the diameters of cysts were measured manually; thus, it could be inaccurate and affected by operator bias. Furthermore, calculated volume of cyst was approximate value and the inter-reader agreement was good for cyst, while the agreements for other imaging parameters were excellent. Future study with software system which can automatically measure the diameters and volume of cyst may help to validate the results of our study. Finally, our study was conducted using only static MRI. Patient movement could potentially lead the fluctuations in the morphology, size and intralesional pressure of the Baker’s cyst, eventually increasing the risk of cyst rupture. In addition, although not included in this study, we believe that future research should include additional imaging parameters such as inferior pointing, which may be related to cyst rupture. Imaging parameters such as width of the neck of the Baker’s cyst, the amount of fluid of the other intra-articular compartments, and the myxoid contents of the cyst are also potentially relevant. Therefore, we consider it valuable to conduct future multicenter studies that take into consideration the dynamic changes occurring in Baker’s cysts, as well as other imaging factors that might contribute to the risk of cyst rupture.Longer transverse diameter and larger volume of Baker’s cyst could be considerable imaging parameters for cyst rupture. Therefore, it could be helpful to mention the transverse diameter of Baker’s cyst in those patients with posterior knee pain to consider the chance of cyst rupture.


Adansonia digitata (baobab), a multipurpose and highly valued tree species, is facing threats due to anthropogenic factors like shifting cultivation practices and fire. The aim of this study was to examine the population structure and phenological attributes of baobab in three districts  in Northwestern Ethiopia. The study was carried out by establishing 17 plots 1 km long and 100 m wide covering a total area of 170 ha in the Quara district and five plots covering 50 ha each in the Kafta Humera and Tselemt districts. Further, plots were subdivided into 25 × 25 m and 5 × 5 m sub-plots for recording other woody species and their regeneration status, respectively. Thirty reproductively matured trees with easily visible crowns were selected to record phenological characteristics and fruit yield. The findings revealed that baobab population was significantly higher in the Tselemt district (3.15 ± 0.15) as compared to Quara (1.43 ± 0.43) and Kafta Humera (1.30 ± 0.23) sites. A bell-shaped diameter distribution was observed in the Quara district and irregular-shaped distributions were observed in Kafta Humera and Tselemt districts. Phenological periodicity and fruit production of baobab did not vary significantly among the three study sites. On average, 404 fruits per tree were recorded with a maximum of 559 fruits in mid-diameter size class trees. Due to livestock browsing, shifting cultivation practices, and uncontrolled fire, the recruitments are limited in the study areas. An in-situ conservation strategy through the plantation and proper management practices are needed to sustain baobab tree species. It is a very long-lived tree and has an average life span of 1000–3000 years with a mean of ca. 2000 years [00 years . Baobab 00 years ,6. The s00 years ,8. It gr00 years .Typically, baobab has functioned as a keystone species making an important contribution to ecosystem functioning and people's livelihoods for food, fiber, and medicine, . All difHowever, the population of baobab has been declining due to different anthropogenic factors like herbivores, fire, unsustainable land conversion, and removal of seedlings on farmlands ,22,26. BDespite their ecological, environmental, and economic benefits in Ethiopia, limited research has been done to examine the population structure and reproductive attributes of baobab tree species in some parts of the country ,31. This22.1The study was conducted in the Quara, Kafta Humera, and Tselemt districts of the Northwestern lowland area of Ethiopia . The thrCombretum-Terminalia woodland vegetation [Vegetation of the study sites are known as the getation . Such wogetation ,35. The 2.2Quick reconnaissance surveys were conducted in each study district to identify where baobab tree species grow and to select representative specific sites that harbor the species. In Quara district at Gelegu kebele, Kafta Humera and Tselemt district at Senasil and Dima kebele were selected respectively and purposively. Each selected growing area of baobab was delineated and prepared grid maps on the desktop study using Google Maps. Ten percent of the delineated area was randomly employed as a sampled plot, which was later verified on the ground to be true.The sampling was designed according to Venter and Witkowski  with sli2.3Data were analyzed using SPSS Statistics version 20 and Microsoft 2010. A one-way ANOVA test was used to assess any significant differences in baobab tree density and fruit yield in the different study districts and diameter and height size classes.Density in different study areas was calculated by summing up all the stems across all sampled plots (abundance) and translating to hectare base for the species encounter in the study plots. Frequency distribution was determined from the number of plots, which a species was recorded (absolute frequency)  and as a33.1Descriptive statistics of the stand density of baobab in the three study areas are presented in In this study, a higher number of baobab tree populations were distributed along the buffer zone of riverine areas, farmland, and homestead land use types . In contThe occurrences of baobab tree species were uniformly distributed in all established sampled plots of Kafta Humera and Tselemt districts (100 %). However, in the Quara district abundant baobab trees occurred only in some established sampled plots (23.33 %) .Balanytus aegyptiaca, Terminalia laxiflora, Ziziphus mucronata, Acacia senegal, Acacia polyantha, Dalbergia melanoxylon, Combretum adenogonium, Tamarindus indica, Terminalia brownie, Acacia brevispica, Combretum molle and Acacia melliferous in the study areas. Tamarindus indica L. is often associated with baobab tree species [Hyphaene petersiana, Ficus carica L. and Sclerocaraya birrea L. [Acacia arenarria, Dichrostachys cinerea, Sclerocarya birrea, Ximenia americana, Striculia africana, Terminalia prunioides, and Combretum imberbe species are associated tree species of baobab. In southern Africa, baobab is associated with Colophospermum (mopane), Cordyla, and Kigelia woodlands in low-lying, dry, hot, and frost-free areas [Baobab tree species were found associated with  species . Neverthirrea L. . Besidesirrea L.  reportedee areas .3.2The population structures of baobab in three-study districts are showed in 3.3Seedlings and saplings of baobab tree species were lacking in the Quara district sampled plots. Livestock browsing, trampling, and shifting cultivation (forest clearing) practices are the major causal factors for the poor sustainability of baobab recruitment. Similarly, Abere et al.  reported3.4Baobab has shown six phenophases for its leaf, flower, and fruit periodicity. These phenophases of the baobab tree are presented in The longest Phenological phase was observed from fruiting initiation to harvesting lasting 165 days, whereas the shortest phenophase was flowering, less period existed only for 105 days . The leaS. setigera in the Metema district, Northwestern Ethiopia was observed to peak in late December and early January. Those results argued that baobab fruits are harvested from May to October in Kenya [Fruiting is the longest Phenological phase, which starts initiation from the first week of October up to mid of November . The higin Kenya . In genein Kenya  also repin Kenya  stated tin Kenya  reviewedin Kenya  and Fennin Kenya  displaye3.5The number of fruits produced per tree did not significantly vary between study districts (P = 0.75). In contrast, Peters  and Asso4The size class distribution of matured baobab trees was bell-shaped in the Quara district and irregularly shaped in Kafta Humera and Tselemt reflecting an unhealthy proportion in baobab, which is not stable in districts region mainly due to different anthropogenic factors in Northwestern Ethiopia. Our results indicate a lack of recruitment in the Quara district along with a few numbers in Kafta Humera under shrublands. Better recruitment of the species was noticed in the Tselemt district along the Tekeze River (an inaccessible area from browsers and grazers). The Phenological variations of baobab were not observed between three districts in two consecutive years. The shortest pheno-phase was noticed for flowering that existed only for 105 days from the third week of August–October, whereas, the longest pheno-phase was observed from fruit initiation to harvesting that took 165 days from October–January. The leafing pheno-phase was in between that took 135 days from the third weeks of April to the second weeks of September. Baobab fruit production is not significantly varied between harvested years and study districts. On average 404 numbers of fruits are produced per tree. Higher numbers of fruits are produced in the middle diameter size classes, which are compared with lower and higher diameter size class trees. Finally, the researchers suggest that an in-situ conservation strategy through mass plantation and proper management practices are needed to sustain the distribution of baobab tree species in the study areas.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Data will be made available on request.Melkamu Abere: Writing – review & editing, Writing – original draft, Software, Resources, Project administration, Methodology, Formal analysis, Data curation, Conceptualization. Zewdu Yilma: Writing – review & editing, Visualization, Validation, Investigation, Funding acquisition, Data curation. Tadesse Tsegie: Writing – review & editing, Visualization, Data curation. Abeje Eshete: Writing – review & editing, Software, Project administration, Methodology, Funding acquisition. Asmamaw Alemu: Writing – original draft, Methodology, Formal analysis, Conceptualization.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.