The preterm birth of a child is a sudden event that can disturb the overall family system and its functioning. Many studies have been conducted with the aim of exploring how and the degree to which this event affects the early mother–infant dyadic relationship and maternal well-being, with often mixed findings. The present study investigates the combined effect of preterm birth and parenting stress on mind-mindedness, a parenting dimension that captures how parents represent and treat their children as separate individuals with their own mental states and activities. A hundred and ten mothers and their three-month-old infants  participated in the study. Mind-mindedness was assessed by coding mothers’ comments about infant’s mental states during dyadic face-to-face interaction. Parenting stress was evaluated with the Parenting Stress Index Short Form questionnaire. Mothers of preterm infants reported similar levels of appropriate and non-attuned mind-related comments to mothers of full-term infants. The reported parenting stress levels were also comparable. Interestingly, only mothers of preterm infants who reported higher stress in parenting showed more non-attuned comments during the interaction. The results underline the need to address preterm birth as a complex event, going beyond group differences and considering its interplay with other risk or protective factors in shaping children’s and parents’ adjustments and well-being. The unexpected end of a pregnancy that culminates in a preterm (PT) birth represents a risk for the infant but also for the mother and the dyad. Many PT infants manifest interactive difficulties, and their mothers seem to be less sensitive to infants’ needs compared to full-term (FT) infants’ mothers . The motThe present study explores how the perceived stress associated with parenting a three-month-old infant interacts with PT birth in affecting a behavioral dimension of parenting that is a direct measure of how the mother is able to represent, understand, and comment on infant mental needs—her mind-mindedness .According to the World Health Organization , an infaPT infants’ characteristics and specific difficulties together with the not-normative parental experience are thought to affect parental well-being and interactive behaviors. This hypothesis has been widely addressed by the literature on PT birth, but the findings, all in all, have failed in providing a clear picture of such an extremely complex phenomenon.A substantial amount of research has focused on how raising a PT infant is a potentially stressful and overly demanding experience, with studies yielding controversial findings ,30,31,32With respect to mothers’ interactive behavior, a large number of studies have reported difficulties for mothers interacting with their PT infants . InvestiSimilar results were found by recent studies addressing the effect of PT birth on maternal mind-mindedness ,42, a beTo sum up, even if PT birth may represent a critical condition affecting dyadic well-being at different levels, divergent findings are present with respect to mothers’ perception of parenting a PT infant as a stressful experience ,31,32,33The current study aims to explore the role of PT birth and the perception of parenting as a stressful experience in maternal mind-mindedness during free-play mother–infant interactions with infants at three months of age. The choice of investigating these relationships at this early age regards both theoretical and practical reasons. Firstly, this is a particularly relevant period for the development of dyadic interaction patterns and co-regulatory processes; secondly, the early identification of difficulties in maternal mind-mindedness can aid in the implementation of effective and appropriately timed clinical protocols and interventions.Since this is the first study to address the topic from this perspective, we consider it explorative. In this sense, the study focuses on a group of mothers of low-risk PT infants heterogenous for gestational age and birthweight and a group of mothers of FT infants.To assess the role of preterm birth condition in maternal mind-mindedness and parenting stress. No differences between mothers of preterm and full-term infants are expected regarding the use of appropriate and non-attuned mind-related comments and in the reported levels of parenting stress.To investigate the relationship between parenting stress and maternal mind-mindedness. We expect that higher levels of parenting stress will be related to lower maternal mind-mindedness , with a stronger effect in the PT group.To examine the interaction between birth condition and parenting stress on maternal appropriate and non-attuned mind-mindedness. We hypothesize that the interaction between PT birth and high levels of parenting stress will negatively affect the quality of maternal mind-mindedness.Based on the literature discussed above, the study aims and expected results are the following:The present study is a cross-sectional study framed in a longitudinal cohort project aimed at investigating the role of preterm birth in the development of mother–infant interactions during the first year of life. The study here presented includes data from the first time point of the cohort project exclusively. The invited participants were 57 PT and 60 FT infants aged three months (corrected age for PT infants) and their mothers. The inclusion criteria for PT infants were having a gestational age between 25 and 37 weeks at birth. The exclusion criteria for the PT and FT groups were the presence of genetic abnormalities, severe neurofunctional impairments, severe neonatal complications and/or neurosensory disabilities , and not having signed the informed consent. Mothers of PT infants eligible for the study were invited by nurses and medical doctors to participate in the study in the postnatal follow-up services of the Neonatal Intensive Care Unit of three main hospitals in northern and central Italy. The mothers of FT infants were contacted in the Maternal and Infant Health Care Services of the same hospitals after delivery. The hospitals agreed to participate in the project due to consolidated research collaborations with the scholars involved in the present study. The PT and FT infants were equally distributed among the three hospitals and were invited to participate in the study over a 1-year data collection period, with the recruitment of participants starting in the year 2017 and ending by January 2019. Seven mothers—three in the PT group and four in the FT group—did not return the requested questionnaires, so they were excluded from the following data analyses. The final sample size includes 110 participants: 54 PT and 56 FT.Both parents signed consensus forms for study participation. All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee  and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.M = 3.02, SD = 0.04; FT: M = 3.01, SD = 0.04), the mothers were invited to participate in the data collection that was the focus of the present study. The data collection consisted of the administration of questionnaires and the video-recording of the mother–infant dyadic interaction and lasted around 20 min. The video-recording session consisted of a three-minute face-to-face interaction with the infant seated in a baby seat and the mother placed in front of him or her facing a mirror located behind the infant’s seat so that both partners’ faces could be clearly seen. The interactions were carried out with similar settings in an appropriate room of each hospital for PT dyads and in the Developmental Psychology Lab of two universities for FT dyads. The mothers were asked to interact with their infants as they would if they were at home. The length of the session corresponded to what was suggested in the 2.2 version of the Mind-mindedness Coding Manual [At three months of infant age  and the number of non-attuned mind-related comments (NAMRC) were used as measures of maternal mind-mindedness. As suggested by Meins and Fernyhough , to contTwo independent observers coded the sessions. Twenty percent of the sessions were selected randomly to test reliability, then coded by both observers. The interrater reliability between the two coders, tested with intraclass correlation, was 0.98 for appropriate comments and 0.86 for non-attuned comments.strongly disagree; 5 = strongly agree) and consists of three subscales, each with 12 items: Parental Distress (PD), Parent–Child Dysfunctional Interaction (P–CDI), and Difficult Child (DC). High values indicate more parenting stress. The Parental Distress subscale explores the stress related to the parent’s perception of her/his child-rearing competences, the level of spousal conflict or support, and the restrictions placed on him or her by the parental role. The Parent–Child Dysfunctional Interaction subscale refers to a parent’s perception of the difficulties in the parent–infant interaction. The Difficult Child subscale items concern the parent’s view of the difficulty of the child’s temperament and demandingness. As some PSI items were unanswered (the maximum number of missing items being 2 for each subject), the subscales and total scale scores were expressed as means. The use of mean scores also allows an easy comparison among PSI subscales. The internal consistency of the current sample was satisfactory and equal to Cronbach’s α 0.86 for PD, 0.86 for P–CDI, and 0.90 for DC.For the study’s aims, the mothers were asked to complete an online version of the Parenting Stress Index Short Form (PSI–SF) questionnaire ,58. The A socio-demographic questionnaire was developed ad hoc for the study’s purposes. The participants were asked to provide information on maternal age, education, and civil status (defined as living with partner or not), as well as on the infant’s birth-order (firstborn vs. laterborn), the presence of siblings (only child vs. with siblings), and the gestational age and the weight at birth.ps < 0.05). Because the data were skewed, we ran the nonparametric tests the Mann–Whitney U and χ2 for preliminary analyses and the nonparametric Spearman’s ρ to test the second hypothesis, and to explore the first and third hypothesis we used the Generalized addicted model for location, scale, and shape (GAMLSS) [Analyses were run with IBM-SPSS version 23  and R software . All the tests were bilateral and the level of statistical significance was set at 0.05. First, the distribution of data was assessed by calculating the variables of skewness and kurtosis. The values for the PSI subscales and AMRC were within reasonable limits, with the skewness ranging from −1.32 to 0.69 and the kurtosis from 0.11 to 1.47. Data for the NAMRC variable were highly skewed (2.29) and high in kurtosis (6.12). The Kolmogorov–Smirnov test indicated that all the variables were not normally distributed ((GAMLSS) . The lat2) explored if differences between groups were present according to the characteristics of the sample.The first preliminary analyses  directed at exploring differences in the use of mind-mindedness comments, both appropriate and non-attuned, and in levels of parenting stress, as assessed with the PSI-SF, in mothers of PT and FT infants.To test the second hypothesis, a set of Spearman’s ρ correlations were used to explore the relationships between mothers’ reported parenting stress scores and their use of appropriate and non-attuned mind-related comments, first taking into account all mothers and, finally, considering the two groups separately.Finally, to test the third hypothesis, the moderating effects of parenting stress on the relationship between birth status and the use of mind-mindedness comments were tested to verify the presence or absence of interaction between the stress of parenting and birth status on maternal appropriate and non-attuned use of mind-related comments. Moderation analyses were performed with the GAMLSS package  using thDescriptive statistics for the mothers’ and infants’ characteristics are reported in SD = 21.69).The mothers of PT and FT infants were similar in terms of age but differed regarding their educational level, with mothers of PT infants showing, on average, fewer years of education than the other mothers. The mothers were all living with a partner, except for one PT infant’s mother. The infants in the PT and FT groups were comparable for gender, birth order, and the presence of siblings, with the majority of the infants recruited being firstborn and only children. The PT infants and FT infants had a mean gestational age of 31.03 and 39.48 weeks, respectively, and a mean birth weight of 1351 and 3342 g, respectively. The PT infants were hospitalized on average for 44.78 days (ps = ns). On average, 11% of the maternal comments referred to infants’ mental state, with 9% of the comments being appropriate for the infant’s ongoing mental activity and the remaining 2% being non-attuned to the infants’ inner state. As for parenting stress, the results showed that the mothers of PT and FT infants reported comparable levels of stress in all the PSI domains.In the following analyses, the relationships among the study’s variables were first investigated on the whole sample of participants, independent of the infant’s birth condition .Appropriate and non-attuned mind-related comments were completely independent, showing correlation values close to zero. Regarding parenting stress, the results showed high and significant correlations among PSI subscales, indicating that the stress levels reported in the parent, child, and dyadic interaction domains were positively related. Regarding the relationship between parenting stress and maternal mind-mindedness, the results indicated that a greater use of non-attuned mind-related comments was related with higher reported stress in the PSI Difficult Child domain. To examine this result further, correlation analyses were conducted separately for the FT and PT groups. B = −0.14, SE = 0.30, p = 0.640) and not-attuned dimensions of maternal mind-mindedness . Considering these findings, the hypothesis of an interaction between birth status and parenting stress, with high levels of parenting stress and PT birth negatively affecting the quality of maternal mind-mindedness, was rejected. To test the moderating effects of child-related parenting stress, as measured by the PSI Difficult Child subscale, on the relationship between birth condition and mind-mindedness, two moderation models were hypothesized and tested with the GAMLSS. The first tested how stress on the PSI Difficult Child subscale moderated the relationship between birth condition (PT vs. FT) and the use of appropriate mind-related comments (AMRC). The second model tested the same effect on the use of non-attuned mind-related comments (NAMRC). Neither model yielded significant results for interactions, thus implying the absence of significant moderation effects of child-related parenting stress (PSI Difficult Child) on the relationship between birth condition and appropriate (PSI DC X birth condition on AMRC: The present study aimed to shed light on the role of PT birth and parenting stress on maternal mind-mindedness, an interactive behavior considered an index of maternal ability to represent and treat the child as a mental agent, which fosters children’s emotional and cognitive development ,60. Our The findings supported our first hypothesis; PT birth condition itself yielded no significant effects on either parenting stress or maternal mind-mindedness. In terms of parenting stress, the results are in line with the conclusions of the more recent literature that failed to find differences between the groups ,30, espeSimilarly, the lack of interference of PT birth per se with the mothers’ ability to view their infants as mental agents corroborates the literature reporting the limited role played by PT birth alone in caregivers’ mind-mindedness ,42 and rAs previous studies evidenced, the characteristics of PT infants may make a difference in this process, with more at-risk samples being more affected . Our stuThe second set of analyses gave a novel contribution to the literature, confirming our second hypothesis regarding stronger effects of parenting stress on mind-mindedness in the PT sample. We not only found a relationship between parenting stress and the quality of maternal mind-mindedness in the whole sample, as previously evidenced by other studies ,64, but Even if the correlations suggested the need for an exploration of the moderation effect, we failed to find support for our third hypothesis. Parenting stress did not interact with PT birth in interfering with the ability to read the infant’s intentions, preferences, emotions and cognitions appropriately. A very recent study examining mind-mindedness predictive factors in PT mothers evidenced the mediating role of environment-driven stress sources, with poorly organized families faced with PT birth—a condition that requires extra effort to rethink the family system and organization—showing fever mind-related comments . This maSome limits of the present study deserve to be mentioned. Firstly, PT infants are a wide and variable population and considering them as a whole group is a limitation. Our sample included mainly low-risk PT infants and healthy mothers, and this did not allow us to explore the role of other infant and maternal individual risk factors, such as the medical condition of both of them, which may make parenting even more challenging. However, our results evidenced that, even in a low-risk sample, some critical aspects of the maternal ability to understand and refer to infants’ mental states may be evidenced and deserve to be explored. Secondly, the role of other environmental and socio-economic factors that were not considered by the present study may affect the quality of parental adjustment, as well as other maternal risk factors that may have also influenced the PT delivery. Finally, we did not consider the role of maternal representations of herself as a mother; the traumatic experience of PT birth; and other behavioral aspects of maternal interaction such as emotional expressions, touch, and the prosody of the voice. The inclusion of these aspects can help us to enrich the understanding of the complex phenomenon of mother–preterm infant interaction. Future studies should explore this phenomenon longitudinally, taking into consideration the role of other individual and dyadic factors as predictors of maternal mind-mindedness ability. Our sample has been collected in only one country even if in different cities, so to generalize the results further explorations in other cultures may be necessary as well as analyses in more at-risk samples.This is the first study to explore both the perception of parenting as stressful and maternal mind-mindedness in a sample of PT and FT dyads. Our results contributed to the literature by suggesting that being a mother of a PT infant is not per se a risk condition. It is when mothers of PT infants report high stress in parenting their infants that the quality of mind-mindedness may be impaired.The conclusion drawn from the study’s findings has relevant clinical implications. In order to fully understand how to prevent PT infants’ and their mothers’ negative outcomes, PT birth must be considered as a complex experience with multifaced implications for parenting. Thus, parenting stress should be considered in the follow-up routines as a crucial risk factor, especially for PT mother–infant dyads. Furthermore, since maternal mind-mindedness is crucial for child development, interventions focused on improving this aspect of maternal interaction should be promoted to prevent future delays in infants and children ,68.


Birth interval duration is an important and modifiable risk factor for adverse child and maternal health outcomes. Understanding the spatial distribution of short birth interval, an inter-birth interval of less than 33 months, and its predictors are vital to prioritize and facilitate targeted interventions. However, the spatial variation of short birth interval and its underlying factors have not been investigated in Ethiopia.This study aimed to assess the predictors of short birth interval hot spots in Ethiopia.The study used data from the 2016 Ethiopia Demographic and Health Survey and included 8,448 women in the analysis. The spatial variation of short birth interval was first examined using hot spot analysis . Ordinary least squares regression was used to identify factors explaining the geographic variation of short birth interval. Geographically weighted regression was used to explore the spatial variability of relationships between short birth interval and selected predictors.Statistically significant hot spots of short birth interval were found in Somali Region, Oromia Region, Southern Nations, Nationalities, and Peoples’ Region and some parts of Afar Region. Women with no education or with primary education, having a husband with higher education (above secondary education), and coming from a household with a poorer wealth quintile or middle wealth quintile were predictors of the spatial variation of short birth interval. The predictive strength of these factors varied across the study area. The geographically weighted regression model explained about 64% of the variation in short birth interval occurrence.Residing in a geographic area where a high proportion of women had either no education or only primary education, had a husband with higher education, or were from a household in the poorer or middle wealth quintile increased the risk of experiencing short birth interval. Our detailed maps of short birth interval hot spots and its predictors will assist decision makers in implementing precision public health. A birth interval is defined as the length of time between two successive live births to the same mother , 2. The A short birth interval is associated with a higher risk of maternal morbidities, including miscarriage, preeclampsia, high blood pressure, and premature rupture of membranes , 5. It iBirth interval practices vary widely around the world . A studyTo the best of our knowledge, no previous study has assessed spatial variation in short birth interval, or predictors of such spatial variation among women in Ethiopia. This implies that the ‘where’ aspect of short birth interval has been inadvertently missed, leading to a significant evidence lacuna. Failure to consider geographic variation in short birth interval, whether it is random, dispersed, or clustered, may result in socioeconomic inequity in public health resource allocation and policy design. Since birth intervals are amenable to policy intervention , it is vEmpirical evidence has documented several risk factors of short birth intervals. These include young maternal age –22, mateNational policies regarding birth control that aim to increase contraceptive uptake (from 42% to 55%) and reduce the total fertility rate (from 4.1 to 3) by the end of 2020 , both ofThe current study aimed to assess predictors of short birth interval hot spots in Ethiopia. The findings of this study will help policy makers, program planners, and other stakeholders in guiding health investment, and prioritize prevention and intervention programs. In addition, mapping short birth interval hot spots will provide a deeper understanding of the impact of past intervention strategies, including family planning services in each region of the country.0–150 N latitude and 330–480 E longitude)  in your submission contain [map/satellite] images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software . For more information, see our copyright guidelines: We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:1.    You may seek permission from the original copyright holder of Figure(s) [2-7] to publish the content specifically under the CC BY 4.0 license. http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:We recommend that you contact the original copyright holder with the Content Permission Form (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0  remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.The following resources for replacing copyrighted map figures may be helpful:http://viewer.nationalmap.gov/viewer/USGS National Map Viewer (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/The Gateway to Astronaut Photography of Earth (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.htmlMaps at the CIA (public domain): http://earthobservatory.nasa.gov/NASA Earth Observatory (public domain): http://landsat.visibleearth.nasa.gov/Landsat: http://eros.usgs.gov/#USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://www.naturalearthdata.com/Natural Earth (public domain): Additional Editor Comments (if provided):Thanks for a very interesting manuscript, please see comments from both reviewers. Looking forward to reviewing your revised manuscript.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Partly**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: Yes**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: The authors have done a commendable job analysis the spatial variability of predictors’ effects on short birth interval across Ethiopia.AbstractOverall well-written abstract, however, I suggest including the meaning of “short” in “short birth interval” in the background/methods sectionMethods• Did any women have more than >2 births during the recall period? How were these dealt with in the analysis?• Add description of how GPS data is collected in the DHS.• Line 48: the definition of what varies?• Line 103: because birth interval is the focus of this analysis, please give a short explanation of how birth interval data were collected in the manuscript, on top of directing readers to the DHS Interviewer’s Manual for further details.• Line 118: I think the authors might be referring to sampling weights here, either way, please specify what weights were applied.• Lines 168-169: Positive, instead of negative, statements should be easier to understand. Rephrase to something along the line of “The model should unbiased…. The residuals should normally distributed and present no spatial patterns.”Results• Line 206: This statement may be misinterpreted, as majority of all births in Ethiopia are in rural areas. Either make this point clear, or present % of short birth intervals by place of residence.• What is the Getis-Ord General G statistic found? What is the distance threshold used for hot-spot analysis?• Lines 266-270: Why did the authors select the middle wealth quintile for comparison? The proportion of households in the middle wealth quintile of an EA can be higher  either for EAs that are relatively poorer/wealthier. This makes the effect of socioeconomic status less apparent.Discussion• First paragraph: I suggest adding the important finding of the variable strengths of the different predictors on short birth interval across Ethiopia.• Second paragraph: Data on both religion and ethnicity can collected in the DHS. Why have they not been considered in the current analysis?• Lines 309-317: And what is the authors’ interpretation of between higher husband education and hot spots of birth interval in Oromia Region, SNNPR and Somali Region?• The discussion will benefit from the authors’ interpretation of the mechanisms through which different predictors act more/less strongly in different places in the country.• In Ethiopia, increased uptake of contraceptives has not translated into reduced birth interval, which may indicate additional unmet need (for limiting and for spacing) among women who have given birth, perhaps due to lack of postpartum counselling or other reasons. The authors may want to comment on this in the current manuscript.Reviewer #2: This is a very interesting and, overall, potentially useful piece of work from the health services planning perspective. I would recommend its publication should the authors clarify some questions. Briefly stated:Major considerationsDespite the moderate coefficient of determination and the values of the statistics used to assess the goodness-of-fit of the different models, I wonder why the authors did not considered (factored in) the following covariates in the models given their likelihood of being associated with (explanatory o predictive variables) short-birth interval: previous 1) multiple pregnancies, 2) miscarriages, 3) c-sections, and 4) previous and current comorbidities. If some of them were associated, the models would incur in an important omitted variable bias, and reported coefficients and results could be biased. The authors must first account for this, and depending on the justification they must then explain in the Discussion the omission and its likely effects on the results.Minor considerationsLines 97-99. Women who had never been married were not included in the study, since women who have multiple births out of wedlock are unlikely to plan their births in the same way as married women.What is the share of women who have never been married in Ethiopia and the different regions? How do women with multiple births out of wedlock plan their births? A substantial share could be biasing the results. This being the casa it should be addressed in the Discussion. Otherwise, it should be so stated.Lines 79-80. Strictly speaking, the formulation of the objective of the study  should not include the methods used to accomplish it  analysis.).**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  10 Mar 2020http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdfEditorial comments: Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at Response: Our manuscript has been revised to meet PLOS ONE's style requirements.http://journals.plos.org/plosone/s/licenses-and-copyright.Editorial comments: 1. We note that [Figure(s) 2-7] in your submission contain [map/satellite] images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software . For more information, see our copyright guidelines: We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:1. You may seek permission from the original copyright holder of Figure(s) [2-7] to publish the content specifically under the CC BY 4.0 license. http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:We recommend that you contact the original copyright holder with the Content Permission Form (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0  remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.The following resources for replacing copyrighted map figures may be helpful:http://viewer.nationalmap.gov/viewer/USGS National Map Viewer (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/The Gateway to Astronaut Photography of Earth (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.htmlMaps at the CIA (public domain): http://earthobservatory.nasa.gov/NASA Earth Observatory (public domain): http://landsat.visibleearth.nasa.gov/Landsat: http://eros.usgs.gov/#USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://www.naturalearthdata.com/ Response: The map of Ethiopia  that was used to develop hot and/or cold spots of short birth interval has been used under the terms of use of the Natural Earth (public domain) , which permits to use the maps in any manner, including modifying the content and design, electronic dissemination, and offset printing. In addition, the geographic coordinates (latitude and longitude) of the clusters in the map were used after getting permission from The DHS Program (https://dhsprogram.com/data/available-datasets.cfm) to use the Ethiopia Demographic and Health Survey data for further analysis and all data are available online upon request. Natural Earth (public domain): The above-mentioned two sources have been acknowledged in all figures . Furthermore, the source of the map has been mentioned in the method section of this revised version of the manuscript as follows (line 109-112). ‘In addition, the administrative polygons of Ethiopia, which were obtained from the Natural Earth [35] has been used to develop the map of hot and/or cold spots of short birth interval. The country’s administrative polygons reflect administrative boundaries, such as regions, zones, and districts of Ethiopia.’Reviewer #1: The authors have done a commendable job analysis the spatial variability of predictors’ effects on short birth interval across Ethiopia.Response: Thank you.Reviewer #1: AbstractOverall well-written abstract, however, I suggest including the meaning of “short” in “short birth interval” in the background/methods sectionResponse: We have now incorporated the meaning of ‘short’ in “short birth interval” in the background section of the abstract (line 18-19).Reviewer #1: Did any women have more than >2 births during the recall period? How were these dealt with in the analysis?Response: When women had more than two births within the five years preceding the survey, birth interval of the most recent births were considered in this current study. The 2016 Ethiopia Demographic and Health Survey report that has been released to the public also followed this approach. In this revised version of the manuscript, we have included a statement describing the inclusion of the most recent birth in the method section of this revised version of the manuscript as follow (line 98-100): ‘When women had more than two births in the five years preceding the survey, birth interval of the most recent two births was considered in this current study.’Reviewer #1: Add description of how GPS data is collected in the DHS.Response: We have incorporated information regarding GPS data collection accordingly (line 101-109):‘Global Positioning System (GPS) receivers were used to collect the location data (geographic coordinates) of each survey cluster. The GPS reading was made at the centre of each cluster. The GPS data collectors ensured the centre was relatively open, away from tall buildings, and out from under tree canopy in order to receive adequate satellite signal strength. To maintain respondents’ confidentiality, GPS latitude/longitude positions for all survey clusters were randomly displaced. The maximum displacement for urban clusters was two kilometres (km) and five km for 99% of rural clusters. The remaining 1% of the rural clusters were displaced a maximum of 10 km. The displacement was restricted to the country's second administrative level (DHS survey region) so that the points stay within the country [34].’Reviewer #1: Line 48: the definition of what varies?Response: The sentence has been rewritten as follow (line 49):‘A short birth interval is associated with a higher risk of maternal morbidities, including miscarriage, preeclampsia, high blood pressure, and premature rupture of membranes .’Reviewer #1: Line 103: because birth interval is the focus of this analysis, please give a short explanation of how birth interval data were collected in the manuscript, on top of directing readers to the DHS Interviewer’s Manual for further details.Response: We have incorporated information regarding how birth interval data were collected (line 115-125).‘Women’s birth interval data were collected through reviewing the date of birth of their biological children from children’s birth /immunization certificate and/or asking information regarding their children’s date of birth from the women. Birth interval data of women for all their children born live irrespective of their survival status at the time of the interview were collected. For children who had birth certificates, their mothers were asked to confirm the accuracy of the information prior to documenting children’s date of birth. This was done to avoid errors because in some cases the information on the document may be the date when the birth was recorded and not the date when the child was born. When children did not have a birth certificate, information regarding their date of birth were obtained from their mothers. Then, the length of birth interval was computed in months and the data were accessible for further analysis in this form.’Reviewer #1: Line 118: I think the authors might be referring to sampling weights here, either way, please specify what weights were applied.Response: We have now specified the type of weight used as follows (line 141).‘Before performing spatial analysis, the weighted proportion (using sample weight) of short birth interval and candidate explanatory variables (see supplementary Table 1) data were exported to ArcGIS.’Reviewer #1: Lines 168-169: Positive, instead of negative, statements should be easier to understand. Rephrase to something along the line of “The model should unbiased…. The residuals should normally distributed and present no spatial patterns.”Response: The comment is accepted and we have corrected the statement accordingly (line 192).‘The model should be unbiased (heteroscedasticity or non-stationarity). The residuals should be normally distributed and revealed no spatial patterns.’Reviewer #1: Line 206: This statement may be misinterpreted, as majority of all births in Ethiopia are in rural areas. Either make this point clear, or present % of short birth intervals by place of residence.Response: We are afraid that the statement was not misinterpreted (line 229). We had already computed the column percentage and presented the percentage of short birth interval by place of residence in the previous version of the manuscript. The finding of the study showed that the majority (94.0%) of women with short birth interval in Ethiopia resided in rural areas. Would you please see the statement again? ‘Among women who experienced short birth interval, 94.0% resided in a rural part of the country.’For further information, please refer to Table 1.Reviewer #1: What is the Getis-Ord General G statistic found? What is the distance threshold used for hot-spot analysis?Response: We have included the finding of Getis-Ord General G test and the distance threshold used for hot-spot analysis as follow (line 236-239): ‘The Getis-Ord General G statistic revealed the presence of high clustering . The average distance at which a feature (cluster in this case) has at least one neighbour was 18 km. The maximum distance at which clustering of short birth interval rate peaked was at 122 km.’Reviewer #1: Lines 266-270: Why did the authors select the middle wealth quintile for comparison? The proportion of households in the middle wealth quintile of an EA can be higher  either for EAs that are relatively poorer/wealthier. This makes the effect of socioeconomic status less apparent.Response: At the variable selection phase of our analysis (using Exploratory Regression tool), it was only the middle wealth quintile that fulfilled the assumption of the ordinary least squares (OLS) (line 188-192). That is why it was included in the model. As it is described in the method section (line 127-132), each wealth quintile was among the candidate explanatory variables that were considered in the Exploratory Regression of the current study .Reviewer #1: First paragraph: I suggest adding the important finding of the variable strengths of the different predictors on short birth interval across Ethiopia. Second paragraph: Data on both religion and ethnicity can collected in the DHS. Why have they not been considered in the current analysis?Response: We accept the comment and have incorporated those findings accordingly (line 305-308): ‘The GWR coefficients of the two strong predictors of short birth interval across Ethiopia, for instance, range from 0.325643 to 0.727715 for women with no education and from 0.24926 to 1.114590 for women with primary education.’ Yes, data on both religion and ethnicity were collected in the DHS. However, in our study, the variables did not satisfy the criteria of properly specified Ordinary Least Squares (OLS) models in the Exploratory Regression tool (line 188-194). On the other hand, those predictors identified in the current study  were the ones with the highest adjusted R2 (adjusted R2=0.64) and met all the requirement of OLS. A search of peer-reviewed articles and grey literature showed a dearth of information on the association between ethnicity and birth interval experience in Ethiopia. The authors have also recommended (line 404-405) for further studies that assess the cultural factors affecting the geographic variation of short birth interval.Reviewer #1: Lines 309-317: And what is the authors’ interpretation of between higher husband education and hot spots of birth interval in Oromia Region, SNNPR and Somali Region?Response: We have refined our previous justification and incorporated the additional reasons for the observed finding as follows (line 337-346). ‘It is possible that husbands with higher education possess knowledge of family planning methods, might encourage their partner to seek family planning services, and support optimum birth interval practice, which might account for the low proportion of short birth interval (cold spots) in Tigray Region and Amhara Region. On the other hand, women whose husbands had attended a higher level of education had a positive relationship with the hot spots of short birth interval in Gambella Region and western Oromia Region. The possible reasons for the observed finding in Gambella Region could be due to the low contraceptive prevalence rate in the region [58]. Further in-depth qualitative study is required to understand the finding in the western Oromia Region.’Reviewer #1: The discussion will benefit from the authors’ interpretation of the mechanisms through which different predictors act more/less strongly in different places in the country.Response: We agree with the reviewer. In addition to the implication of each finding of the current study discussion for each predictor of short birth interval, we have added the following statement (line 364-372): ‘In this study, it was found that different predictors of short birth interval  act more/less strongly across regions. For instance, women not attending formal education or attending primary education only had a strong positive relationship with hot spots of short birth interval in Somali Region while they had a week positive association with short birth interval in Amhara and Tigray region. This might be related to variations in the availability and accessibility of different family planning services and cultural variation across administrative regions of the country.’Reviewer #1: In Ethiopia, increased uptake of contraceptives has not translated into reduced birth interval, which may indicate additional unmet need (for limiting and for spacing) among women who have given birth, perhaps due to lack of postpartum counselling or other reasons. The authors may want to comment on this in the current manuscript.Response: The information that shows the increase in uptake of contraceptives in Ethiopia over time but the unchanged birth interval has been obtained from previous literature . ‘Moreover, despite the increasing trend in contraceptive utilization in Ethiopia, from 5.9% in 2000 to 14.0% in 2005, 27.0% in 2011 and 35.0% in 2016, the prevalence of short birth interval has remained unchanged, 19.7% in 2000, 21.4% in 2005, 20.5% in 2011 and 21.7% in 2016 [15-18].’There could be individual-, household- and community-level factors that are responsible for the above-mentioned findings. Since the objective of the current study was to assess the predictors of short birth interval hot spots in Ethiopia, and it is beyond the scope of the current study to comment on that. Literature has also shown that modern contraceptives are effective at preventing conception; what is not understood is why, in practice, their use may not always result in longer birth intervals or preventing short birth interval : 205–214). Even though women who use contraceptives increase over time unless they took the contraception to achieve an optimum birth interval (as per the WHO recommendation) the magnitude of short birth interval may not be reduced. It could also be associated with improper contraceptive use, which may end up with unintended/unplanned pregnancy and as a result a short birth interval. Generally, the issue of why the increase in trend of contraception use over time in Ethiopia did not result in reducing the magnitude of short birth interval  is complex and beyond the scope of the current study. The authors believe that it requires further studies  to comment on the underlying factors responsible for the observed findings.We also would like to thank you for raising this issue and will consider it for further study in the future. Reviewer #2: Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.Response of reviewer #2: PartlyResponse: For further clarification, the conclusion has been rewritten as follow (line 386-387): ‘Overall, the study illustrated that there was a spatial variation of short birth interval among women in Ethiopia. Short birth interval hot spots were identified in Somali Region, Oromia Region, SNNPR and a few parts of Afar Region. Being a resident in a geographic area with a high proportion of women having no education or primary education, husbands who had attended higher education and households from a poorer or middle wealth quintile increased the risk of experiencing short birth interval.’Reviewer #2: This is a very interesting and, overall, potentially useful piece of work from the health services planning perspective. I would recommend its publication should the authors clarify some questions. Briefly statedResponse: Thank you.Reviewer #2: Major considerationsDespite the moderate coefficient of determination and the values of the statistics used to assess the goodness-of-fit of the different models, I wonder why the authors did not considered (factored in) the following covariates in the models given their likelihood of being associated with (explanatory o predictive variables) short-birth interval: previous 1) multiple pregnancies, 2) miscarriages, 3) c-sections, and 4) previous and current comorbidities. If some of them were associated, the models would incur in an important omitted variable bias, and reported coefficients and results could be biased. The authors must first account for this, and depending on the justification they must then explain in the Discussion the omission and its likely effects on the results.Response: We appreciate your observation. In order to consider these particular variables  as potential factors, data regarding the presence/absence of the aforementioned events before the birth of the index child should be collected. However, these variables were not collected in the Ethiopia Demographic and Health Survey. In this revised version of the manuscript, the implication of not including some of these variables has been included. The authors, however, believe that it would not be relevant to consider the history of abortion as one of the potential predictors. Because the most recent WHO recommendation for a healthy pregnancy interval after abortion is six months , which could fall under short birth interval category while it is not in reality. Therefore, considering this variable as one of the potential factors could be misleading. Regarding comorbidities, it would have been good to include the comorbidity status of women at/after the birth of the preceding child (not at the birth of the index child) as a predictor. Nevertheless, the data were not available in the 2016 Ethiopia Demographic and Health Survey. As a result, it was not included in the analysis. To acknowledge some of the above limitations of our study, the following statement has been included in this revised version of the manuscript (line 376-380): ‘In addition, the EDHS did not collect data regarding the maternal previous history  of multiple pregnancies, caesarean section, and comorbidities, which could be potential predictors for the spatial variation of short birth interval. Therefore, the interpretation or conclusion based on this study should consider these limitations.’Reviewer #2: Minor considerationsLines 97-99. Women who had never been married were not included in the study, since women who have multiple births out of wedlock are unlikely to plan their births in the same way as married women.What is the share of women who have never been married in Ethiopia and the different regions? How do women with multiple births out of wedlock plan their births? A substantial share could be biasing the results. This being the casa it should be addressed in the Discussion. Otherwise, it should be so stated.Response: First of all, the total number of women who had never been married but eligible to provide birth interval data was small . With regard to their sample size, excluding these women is less likely to bias the findings of the study. Second, literature has shown that marital status of women had a contribution to the differences in the prevalence of postpartum family planning use among women  3:1). The study performed by Gebremedhin AY. et al., 2018 also pointed out that the difference in postpartum family planning use among married and not married women could be associated with their difference in risk perception related to unwanted or mistimed pregnancy, which is expected to be high among married women than none married ones. Finally, having multiple children out of wedlock in a culturally conservative society, like Ethiopia, is not common. Though it requires peer-reviewed evidence, the primary author knows the study area very well and understand the relationship between marital status and birth interval issue in the country. For further clarity, the number of women who had never been married and excluded from the analysis (n=12) was specified in the method section of this revised version of the manuscript (line 96).Reviewer #2: Minor considerationsLines 79-80. Strictly speaking, the formulation of the objective of the study  should not include the methods used to accomplish it  analysis.).Response: We agree with the reviewer and have deleted the statement that specifies the methods used to accomplish the objective. It is rewritten as follows (line 79):‘The current study aimed to assess predictors of short birth interval hot spots in Ethiopia.’AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 24 Apr 2020PONE-D-19-32257R1Application of Geographically Weighted Regression analysis to assess predictors of short birth interval hot spots in EthiopiaPLOS ONEDear Mr. Shifti,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.We would appreciate receiving your revised manuscript by Jun 08 2020 11:59PM. When you are ready to submit your revision, log on to If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocolsTo enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.We look forward to receiving your revised manuscript.Kind regards,Charles A. Ameh, PhD, MPH, FWACS (OBGYN), FRCOGAcademic EditorPLOS ONEAdditional Editor Comments (if provided):Thanks for a comprehensive and satisfactory response to most of the reviewers comments. One questions is still unresolved: How did you deal with the analysis of women with more than 2 births during the recall period?[Note: HTML markup is below. Please do not edit.]https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool,  11 May 2020Thanks for the constructive feedback. When women had more than 2 births during the recall period , birth interval of their most recent two births, which is birth interval between the index child and the immediately preceding child of women was uniformly considered for all the study participants. The 2016 Ethiopia DHS in its report released to the public also considered birth interval information from women’s most recent two births   [Ethiopia] and ICF. Ethiopia Demographic and Health Survey 2016. Addis Ababa, Ethiopia, and Rockville, Maryland, USA: CSA and ICF. 2016.). In this revised version of the manuscript (line 98-101), the inclusion of women’s birth interval from their most recent two births is described as follow: ‘When women had more than two births in the five years preceding the survey, birth interval of their most recent two births  was uniformly considered for all the study participants.’https://pacev2.apexcovantage.com/.All figures are uploaded to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 13 May 2020Application of Geographically Weighted Regression analysis to assess predictors of short birth interval hot spots in EthiopiaPONE-D-19-32257R2Dear Dr. Shifti,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,Charles A. Ameh, PhD, MPH, FWACS (OBGYN), FRCOGAcademic EditorPLOS ONEAdditional Editor Comments :All comments have been satisfactorily addressed. CongratulationsReviewers' comments: 20 May 2020PONE-D-19-32257R2 Application of Geographically Weighted Regression analysis to assess predictors of short birth interval hot spots in Ethiopia Dear Dr. Shifti:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Charles A. Ameh Academic EditorPLOS ONE


Maternal education represents one of the most important social determinants of inequality in birth weight (BW) in developing countries. The present study sought to investigate secular trends in health inequality considering the difference in mean BW between extremes of maternal educational attainment in Brazil. Using a time-series design, data from 6,452,551 live births which occurred in all Brazilian state capitals from 1996 to 2013 were obtained from the Information System on Live Births. Secular trends of the difference in mean birth weight between low (<8 years of schooling) and high (≥12 years of schooling) educational attainment were analyzed. The main finding was that differences in mean birth weight between the two extremes of maternal educational attainment decreased over time. There was a significant decrease in mean BW in neonates born to mothers with higher educational attainment, and a slight increase in those born to mothers with lower educational attainment. One of the key factors involved in decreasing inequality was an increase in the number of antenatal visits. In view of these results, we conclude, that despite a slight increase of mean birth weight among mothers with low education, the reduction of inequality in pregnancy outcomes over time in Brazil is attributable to a worsening scenario for mothers who are better off rather than to improvements for the most vulnerable group of mothers. Individuals in unfavorable socioeconomic conditions are more vulnerable to adverse physical and mental health outcomes compared to those who are better off2.Several demographic and socioeconomic conditions influence birth outcomes. Among them, ethnicity, education, occupation, income, social class, the availability of housing, urban infrastructure, social support, and exposure to crime have all been described4. At the individual level, access to health care, medical practices, behavioral factors, and stress are also related to birth weight6.The impact of social inequalities on human health is well established, and has shown increasing relevance in developing countries. Thus, in these countries, it is important to encourage social and economic development policies which, together with public health programs, may favorably influence perinatal outcomes, particularly birth weight7. In Brazil, we have shown in a previous study, despite significant improvements in maternal education, the rate of LBW remained stable around 8.5% of all life births during the last 15 years8. In Brazil, this situation regarding LBW is considered an epidemiological paradox and, according to some researchers, it can be explained by several factors, among them, the underreporting in the registry of low birth weight in the poorest and most vulnerable regions and, at the same time, the intense use of health care technologies such as cesarean sections and assisted reproduction techniques in other wealthier regions with more favorable socioeconomic conditions in the country9.Maternal education is a strong determinant of birth weight acting through a number of mediators such as adequate access to information, health care and nutrition10. Biological, demographic, socioeconomic, and environmental factors during pregnancy have a significant influence on birth weight14. Among these, maternal social integration is considered one of the most relevant. Mothers exposed to stress are more likely to engage in high-risk behaviors such as smoking, alcohol intake, and psychoactive drug use, and are more likely to be overweight or obese—all factors which have been associated with lower birth weight15. Maternal education is also among the most relevant social determinants of child health; mothers with low educational attainment are at higher risk of delivering low birthweight infants17.Birth weight has impacts that persist throughout the life cycle, and its determinants are many18. However, some recent studies have found that mean birth weight has declined in some developed countries, although specific causes have not been identified19. Therefore, mean birth weight has presented different secular trends among different countries, under the influence of several determinants.Average birth weight has increased in many countries over the last three decades, due to improved access to antenatal care and population-wide improvements in socioeconomic condition20. This rate is strongly influenced by sociodemographic factors and by access to adequate health care, and thus reflects high inequality among the different social classes and geographic regions of the country. However, the assessment of rates of low birth weight alone is not able to show the small impacts of the various individual social determinants of birth weight over time21.Brazil has one of the highest rates of low birth weight among developing countries, at approximately 8,0% and remaining stable over the last 10 yearsTherefore, the objective of this study is to evaluate the influence of inequality between extremes of maternal education on birth weight, considering the trend of absolute and relative differences in mean birth weight over time among mothers with higher and lower educational attainment in an 18-year time series (1996–2013) in Brazil.Sistema de Informação sobre Nascidos Vivos, SINASC), which covers 96% of all live births in Brazil22. This open-access database is available through the Ministry of Health website (http://datasus.saude.gov.br) or directly on the Health Information page of the Unified Health System Department of Informatics – DATASUS (http://datasus.saude.gov.br/informacoes-de-saude/tabnet).This time-series study included all live births which occurred in 26 Brazilian state capitals and the Federal District from 1996 to 2013. Data were obtained from the Information System on Live Births  over time, presented as a continuous variable, were the outcome of interest. The investigated variable, maternal educational attainment, was dichotomized into two extremes: low and high . Thus, extreme levels of maternal education were used because we understand that these categories are more subject to the potential impact of access to health services and technologies during antenatal and perinatal care on birth weight25.The following covariables were considered: maternal age , number of previous live births (0 or ≥1), number of antenatal visits , gestational age (˂37 or ≥37 weeks), and mode of delivery . State capitals were grouped by the five geographic regions of BrazilBirth weight means were calculated yearly for each Brazilian capital. The absolute and relative differences in mean birth weight between the two extremes of maternal education were calculated to assess the inequality between them.26 for the years 1996 to 2003 and 2004 to 2013. We split in two periods of time after analysis using Joinpoint Regression Program Software Environment (version 4.3.1). The variables year and geographical region of birth were entered into the initial (standard) model (Model a). The covariables maternal age (Model b), number of children (Model c), number of antenatal visits (Model d), gestational age (Model e), and mode of delivery (Model f) were sequentially included.The annual means of birth weight differences between the two extremes of maternal education was estimated using a linear mixed modelStatistical analysis was performed in PASW Statistics, Version 18.0 , with a 5% significance level and 95% confidence intervals (CIs).The study protocol was approved by the Research Ethics Committee of Hospital de Clínicas de Porto Alegre (Brazil) with opinion number 16–0338. The study was carried out in accordance with national and international guidelines.During the study period, there was a significant reduction in adolescent pregnancies. There was also an increase in cesarean sections among mothers with low educational attainment, which, by the end of the period, was equivalent to approximately half of the percentage observed among mothers with high educational attainment. The descriptive variables used in the study, including maternal socioeconomic conditions, number of previous live births, number of antenatal visits, percentage of pregnancies in adolescence, cesarean sections, and preterm deliveries, are shown in Table The findings point out a gradual decrease in the frequency of women with low educational attainment, from 55.4% in 1996 to 18.5% in 2013. Accordingly, there was an increase in the frequency of women with high educational attainment, from 7.2% in 1996 to 24.4% in 2013  reduced the inequality between birth weight means in the two extremes of maternal education. Maternal age (Model b) had a negative effect, mainly in the second period (2004–2013), increasing the inequality in means of birth weight between the two extremes of maternal education. The covariables number of children, gestational age, and mode of delivery did not show any effect on the differences in birth weight means between the two groups of educational attainment during the study period.In both periods, the number of antenatal visits 40. Likewise, changes in the profile of pregnant women in the country, with an increase in the number of mothers aged 35 or older, have increased the risk of pre-existing health conditions and complications during pregnancy, such as hypertensive disorders41. This factor could be related to the decrease in mean birth weight observed, and has been previously described as the “low birth weight paradox”, whereby better socioeconomic development is associated with a higher rate of low birth weight28.Preterm births also have played a role in the birth weight trends observed herein, especially in the group of mothers with higher educational attainment. A study that evaluated preterm births between 2000 and 2010 in the most developed areas of Brazil suggested that successful interventions increased the rate of preterm live births by 45.2%Limitations of this study include the lack of information about preexisting maternal clinical background, obstetric diseases, and intercurrent events during pregnancy. Data on pre-gestational body mass index, smoking, alcohol intake, psychoactive drug use, and maternal nutrition were not available. Inaccurate recording of gestational age in weeks and the high rate of incompleteness of the variable race/skin color made the inclusion of these variables in the study impossible.On the other hand, the national scope of this study, the number of live births included in the analyses (more than 6 million) and its representativeness within the Brazilian population, the 18-year period of analysis (from 1996 to 2013), and the acknowledgment of maternal obstetric characteristics associated with birth weight are among the strengths of this study.20. Social advances and improvements in maternal education and maternal and child care have failed to exert a positive impact on birth weight, probably due to increased medical and technological interventions at all maternal education levels. Besides, the limited change in mean birth weight observed among infants born to women in unfavorable socioeconomic conditions may suggest that advances have not reached the most vulnerable strata of society.These results reflect the demographic, epidemiological, and perinatal transitions in the country over the last two decades, which have had an impact on mean birth weight. Similar trends have been reported in other countries, such as the United States and China, with decreases in birth weight in the last yearIn conclusion, despite a slight increase of mean birth weight among mothers with low education, this study indicates that the reduction of social inequalities in birth weight in Brazil came at the expense of worse outcomes in the better-off group, as opposed to improvements in mothers with low educational attainment. These findings suggest that the current epidemiological profile of birth outcomes in Brazil is characterized by the presence of “equality in inequality”, whereby similar outcomes occur as a result of differential effects of interventions and different social scenarios, leading to a merely apparent reduction of social inequality between extreme social strata.Finally, the results found allow us to affirm that the reduction of inequality in pregnancy outcomes over time in Brazil is mostly attributable to a worsening scenario for mothers who are better off rather than to improvements for the most vulnerable group of mothers.


In patients with upper gastrointestinal bleeding and hemorrhage originating from the major duodenal papilla pseudoaneurysm associated haemosuccus pancreaticus (HP) is a rare differential diagnosis which should be considered. Diagnosis may be challenging, as clinical presentation is often unspecific with only intermittent hemorrhage. Treatment of the causal pseudoaneurysm is mandatory and endovascular coil embolization is the suitable first-line management strategy.Until now there are only a very few studies about this clinical picture and its therapeutic options, especially data regarding whether additional fluid embolization is beneficial/necessary in HP is currently lacking.We report a case of a 59-year-old male patient with chronic pancreatitis and haemosuccus pancreaticus caused by a pancreatico-arterial fistula with an associated inflammatory pseudoaneurysm of the splenic artery. Initially we sought to embolize the pseudoaneurysm with microcoils. As only one coil could be safely deployed in the pseudoaneurysm we additionally employed tissue adhesive embolization in order to achieve complete occlusion of the pseudoaneurysm as well as the pancretico-arterial fistula. In the presented case inflammatory levels decreased following embolization, possibly linked to a decline in pathologic excretion of elastase and autodigestion. As not only the pseudoaneurysm but also the underlying fistula were occluded, the risk of recurrence may conceivably be reduced.Diagnosis of HP is difficult and treatment of the causal pseudoaneurysm is mandatory. Endovascular embolization is the suitable first-line management strategy, complete occlusion of the fistula should be considered when possible. Haemosuccus pancreaticus (HP), a rare cause of upper gastrointestinal bleeding  , initial computed tomography of the abdomen was deemed unremarkable. Esophagogastroduodenoscopy detected an active hemorrhage from the major duodenal papilla, which could not be reproduced in the following angiography. As the cause of haemosuccus pancreaticus remained unclear, the patient was transferred to our maximum care hospital for further diagnosis and treatment of the upper gastrointestinal bleeding.Repeat esophagogastroduodenoscopy showed gastric varices but was otherwise unremarkable. During re-evaluation of the initial computed tomography a pseudoaneurysm of the splenic artery was discovered, sizing 7 × 8 × 9 mm Fig. .Fig. 1PAngiography was performed again to verify and potentially embolize the pseudoaneurysm. The splenic artery was catheterized selectively with a 4 Fr catheter via right femoral access. Initial angiogram demonstrated spontaneous occlusion of the pseudoaneurysm. As both clinical and laboratory signs of hemorrhage had persisted the days prior to intervention, decision was made to super-selectively catheterize and potentially embolize the presumably occluded aneurysm. Angiogram following successful catheterization revealed a fistula between the pseudoaneurysm and the main pancreatic duct Fig. .Fig. 2MDue to pre-existing spontaneous partial thrombosis only one microcoil  could be safely placed within the aneurysm. In order to completely occlude the pancreatico-arterial fistula additional tissue adhesive embolization was performed by Histoacryl /Lipiodol ; ratio 1:5; 0,4 ml). Distribution of tissue adhesive in the pseudoaneurysm and fistula is demonstrated in Fig. Final angiogram confirmed complete obstruction of the pseudoaneurysm, as well as preserved regular perfusion of the splenic artery. Subsequent follow-up computed tomography performed 4 days and 10 months after embolization demonstrated hyperdense tissue adhesive in the fistula/aneurysmal sac as well as persistent occlusion of the pseudoaneurysm. The postinterventional course was uneventful and the patient was discharged in the following days. He was re-admitted 6 months after initial intervention: Endoscopy revealed bleeding from gastric varices, the papilla appeared unremarkable.Haemosuccus pancreaticus is a rare complication of acute or chronic pancreatitis, predominantly observed in men (sex ratio 7:1), associated with chronic alcohol consumption  may be excluded. Contrast enhanced computed tomography allows for reliable detection of pancreatic pathologies, as well as the assessment of potential complications of chronic pancreatitis while visualizing the peripancreatic vessels. Finally, angiographic intervention (including coil/glue embolization) is the therapy of choice for gastrointestinal bleeds not manageable by endoscopy (Yoshida et al. The probability of a recurrent bleeding after catheter assisted embolization varies between 0 and 30% depending on the reference literature (Vimalraj et al. In patients with persistent unstable hemodynamics, recurrent bleeding or failed embolization, surgical management should be instituted without delay (Vimalraj et al. In patients with upper gastrointestinal bleeding and hemorrhage originating from the major duodenal papilla pseudoaneurysm associated HP is a rare differential diagnosis which should be considered. These patients are difficult to manage, frequently present with recurrent bleeding and have a high mortality rate. Treatment of the causal pseudoaneurysm is mandatory and endovascular embolization is the suitable first-line management strategy, complete occlusion of the fistula should be considered when possible.


In Table 1 of the above article, the values for `Singleton' and `Multiple birth' in 2003 were inverted. This has now been corrected as follows:2003Type of BirthSingleton 3494 (96.0)Multiple birth 145 (4.0)


We report the case of a preterm small for gestational age male infant born at 24 weeks of gestation with a birth weight of 268 g who was discharged from our hospital without the requirement for home oxygen therapy or tube feeding. He did not experience severe intraventricular hemorrhage, periventricular leukomalacia, hearing disability, or any other serious complications. At that time (February 2019), according to the University of Iowa's Tiniest Babies Registry, he was the tiniest male infant in the world to survive without any serious complications other than severe retinopathy of prematurity that required laser therapy. Although the survival rate of infants with extremely low birth weight is improving worldwide, a high mortality rate and incidence of severe complications remain common for infants weighing <300 g at birth, particularly in male infants. In recent years, there have been frequent discussions regarding the ethical and social issues involved in treating extremely preterm infants weighing <400 g. Despite the challenges, reports of such infants surviving are increasing. Neonatal medicine has already achieved great success in treating infants weighing 400 g or more at birth. However, lack of evidence and experience may make physicians reluctant to treat infants weighing less than this. The present case demonstrates that intact survival of a marginally viable male infant with a birth weight of <300 g is possible with minimal handling and family involvement beginning shortly after birth. Our detailed description of the clinical course of this case should provide invaluable information to physicians around the world who treat such infants. This report will aid in the progress of neonatal medicine and help to address many of the social and ethical issues surrounding their care. Detailed case reports of infants with a birth weight of <300 g are extremely limited because of their exceedingly low survival rate –9. In paNeonatal medicine has already achieved great success in caring for infants weighing 400 g or more at birth , 3. HoweWe report the case of a preterm small for gestational age male infant who was born at 24 weeks of gestation with a birth weight of 268 g and was discharged from our hospital without requiring home oxygen therapy or tube feeding. He did not experience severe intraventricular hemorrhage, periventricular leukomalacia, hearing disability, or any other serious complications. This case illustrates the importance of both minimal handling and family involvement.The concept of minimal handling has been familiar to pediatricians since 1980 –18. TodaFamily involvement is the standard of care for premature infants admitted to the newborn intensive care unit (NICU) and can be regarded as the essential supporting foundation of NICU treatment. It strengthens bonds among family members, reduces stress for both the babies and their families, and promotes infant stability and development –21. Despvia natural insemination. At 23 weeks of gestation, the mother was referred to our hospital because of severe fetal growth restriction caused by utero-placental insufficiency and was treated with antenatal steroids. Fetal maturity was ascertained by calculating from the mother's last menstrual period and was confirmed by prenatal ultrasound. Prenatal counseling was conducted for the parents, and they requested to give birth by cesarean section. At 24 weeks and 0 days of gestation, the infant was delivered by emergency cesarean section because of interrupted blood flow in the umbilical cord; there was no umbilical cord coiling or amniotic fluid staining. The weight of the placenta was 60 g. Placental pathology revealed infarction. No findings of chorioamnionitis were observed. Immediately after birth, he was wrapped using a plastic bag on a prewarmed radiant warmer. The ambient temperature of the operating room was set to 27°C  who became pregnant  to 27°C . He was pressure , 29. PDApressure . He was via an 18G umbilical venous catheter. After this catheter became occluded on day 12, a 27G peripherally inserted central venous catheter was used, but it also became occluded on day 19. From then on, parenteral nutrition was continued via a peripheral venous catheter. On day 1, oral administration of the mother's breast milk using a cotton swab was performed by the parents, and trophic feeding via nasogastric tube was started. A maximum of 3 mL/kg of 5-fold-diluted amidotrizoic acid was rectally administered for 1 week starting on day 1, resulting in successful defecation. After 3 days of trophic feeds, enteral feeding was stopped because the infant's abdomen was gradually becoming distended. His daily abdominal X-ray indicated significantly expanding intestinal gas, and we diagnosed him with meconium-related ileus. Intragastric administration of 3 mL/kg 5-fold-diluted amidotrizoic acid succeeded in triggering mass excretion of feces, as described in previous studies , and biochemical factors . We performed a comprehensive blood examination  only once every week or two , requiring laser treatment. He was discharged from the hospital on day 176  without any requirement for home oxygen therapy or tube feeding. His body weight at discharge was 3,238 g (−3.41 SD), his head circumference was 35.5 cm (−1.31 SD), and his length was 46.8 cm (−4.55 SD)  (45). ThAlthough neonatal medicine has advanced enough to produce favorable clinical outcomes for most premature infants, physicians still hesitate to treat those weighing <300 g at birth, especially male infants, because of lack of experience and evidence –12. CaseAntenatal steroid treatment contributed greatly to the absence of serious complications in the present case . The absRegarding family involvement during the acute phase of treatment, concerns about infection and instability may lead some physicians to refrain from encouraging families to proactively seek contact with their infants. However, we believe that encouraging families to hold their infants and talk to them contributes to infant stability and improves long-term development –21. The A limitation of this report is that the number of infants weighing <300 g at birth who could survive is unclear. The University of Iowa's worldwide database of surviving infants with birth weights <400 g includes cases reported in media outlets and medical journals, as well as reports submitted directly by physicians, but it is possible that some of those cases may not be included . HoweverOur experience, in this case, demonstrates that minimal handling can be safe and effective in treating infants with birth weight <300 g and that family interaction beginning soon after birth can positively affect clinical outcomes and family relationships with no adverse effects. We conclude that improved clinical outcomes and strong family relationships can be achieved for marginally viable premature infants through meticulous consideration of minimal handling and family involvement together with the application of up-to-date research and advanced medical devices. This report describes a very rare case that could be a source of invaluable information for the development of neonatal medicine. Further research developments are needed.The original contributions presented in the study are included in the article/Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the participants' parents for the publication of this case report and any identifiable data or images.TA was an attending physician of the patient, performed the literature review, and wrote the first draft of the manuscript. DW, ST, and MT assisted in the patient's treatment. MH and TT supervised the patient's treatment, provided scientific contributions, and critically revised the paper. All authors read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Retrobulbar hemorrhage (RBH) is a rare complication of facial trauma that can lead to dangerous orbital compartment pressures and must be rapidly recognized to prevent permanent vision loss. Point-of-care ultrasound (POCUS) offers a rapid modality for evaluating a wide variety of ocular pathologies, and prior case reports demonstrate the ability of clinicians to recognize RBH using ultrasound. This study aimed to assess the ability of clinicians at various stages of training to identify a RBH using POCUS in a cadaveric model. Clinicians also were assessed for self-reported comfort using ultrasound for ocular pathology before and after the study.Participants included 17 physicians who evaluated 10 eyes (from five cadavers) that were independently randomized to have either a modeled RBH or no hemorrhage. Participants’ final diagnosis of each eye was recorded (RBH present or not), and participants also completed pre- and post-activity surveys.The overall sensitivity and specificity to correctly diagnose retrobulbar fluid was 87% and 88%, respectively. Sensitivity and specificity were higher after excluding clinicians in their early phase of training. Additionally, self-reported comfort level with ocular ultrasound was significantly improved by this activity.Emergency physicians at a variety of training levels can correctly identify a cadaveric model of retrobulbar hemorrhage. Use of this cadaveric model can improve exposure of clinicians to the appearance of a rare but vision-threatening ocular pathology such as RBH. Retrobulbar hemorrhage (RBH) is a rare complication of facial trauma; however, it must be rapidly recognized to prevent permanent vision loss from increased orbital compartment pressures.5Cadaver models represent a useful way to simulate rare pathologies for both research and educational purposes.This study was accomplished in the Bioskills laboratory of Northwell Health Systems, using fresh frozen cadavers and in compliance with department policies and institutional review board standards. To prepare the eyes for analysis, 5–10 milliliters (mL) of normal saline was injected into the posterior chamber using a 22-gauge needle to restore the normal anatomic shape (as cadaveric eyes become desiccated). Five cadavers were available for this study, and each eye  was independently randomized to be either normal or have RBH. For the eyes randomized to the RBH group, 10–20 mL of a normal saline and gel mixture (1:1) was instilled posterior to the eye under ultrasound guidance . ParticiEach participant was given a pre-activity survey and a brief instructional introduction on the use of POCUS for ocular pathology and the appearance of RBH on ultrasound. During the introduction, participants were given a 15-minute didactic presentation summarizing techniques for ocular POCUS, representative normal images, and examples of RBH. Each participant had the opportunity to use either a SonoSite M-Turbo ultrasound  equipped with a linear 10 megahertz array, or a Philips Lumify L12-4 linear array  (attached to an Android-based LCD screen) on each cadaveric eye. Participants then recorded the presence or absence of a RBH for each eye. Participants completed a post-activity survey regarding their comfort level with ocular ultrasound and likelihood to use in clinical practice. Following completion of the study, each participant’s surveys and score sheet were given a unique randomized number without additional identifying information.Results of participants’ evaluation of each eye were recorded and analyzed for sensitivity and specificity, and further analyzed by subgroups according to level of training. Additionally, survey responses for all groups were recorded and a comparison was made for each question regarding comfort level and likelihood to use POCUS for evaluation of ocular pathology.In this pilot study, a total of 17 participants evaluated 10 eyes (five cadavers) prepared for this investigation . What do we already know about this issue?Retrobulbar hemorrhage, a rare complication of facial trauma, must be rapidly recognized to prevent permanent vision loss.What was the research question?This study assessed if clinicians could identify a cadaver model of retrobulbar hemorrhage using point-of-care ultrasound.What was the major finding of the study?Emergency physicians could accurately identify the ultrasound findings of a retrobulbar hemorrhage in a cadaver model.How does this improve population health?This model can improve the familiarity of clinicians to the ultrasound findings seen in patients with retrobulbar hemorrhage.The participants were able to distinguish those eyes with a modeled RBH from “normal” anatomy, with an overall sensitivity and specificity of 0.87 and 0.88, respectively . This inThe participants reported their comfort level with using physical exam and POCUS for evaluating ocular pathology before and after the exercise, using a five-point Likert scale. Both saw statistically significant increases in comfort level after completion, based upon an increased, self-reported comfort level.RBH is a rare but potentially devastating injury that must be rapidly recognized to treat effectively; however, concomitant craniofacial injuries can affect an examiner’s ability to recognize signs of RBH on physical exam. Additionally, the time associated with obtaining and reading CT images can lead to dangerous delays in diagnosis. POCUS can be used to rapidly screen for RBH at the patient’s bedside and without the patient having to leave the department for imaging. Previous case reports have documented the use of POCUS to identify RBH; however, the rarity of this pathology has made more systematic research difficult.Our pilot study indicates that human cadaver models can be used to effectively train emergency medicine practitioners to recognize sonographic signs of a RBH. After the completion of a focused training session, the participants successfully identified a RBH on ultrasound with a sensitivity and specificity that increased with the level of postgraduate training. We noted a sensitivity of 0.96 and a specificity of 0.94 with recognizing RBH in those PGY-3 level of training or higher. Physicians currently enrolled in the ultrasound fellowship who participated in this study had a sensitivity and specificity of 100%, suggesting that more advanced training can further increase the diagnostic utility of ocular ultrasound. Attending scores decreased slightly to 0.92 (sensitivity and specificity), likely reflecting higher proficiency among ultrasound fellows with more recent, advanced training.Using our pre- and post-study questionnaires, our study showed a significant increase in participants’ comfort level in using POCUS to diagnose RBH. Physician likelihood to use ocular ultrasound was unchanged from the activity; however, given that the ranking was initially high (4 out of 5), any increase in likelihood-to-use may not be measurable with the low sample size obtained. Based upon these findings, fresh frozen cadavers can provide an accurate educational simulation of RBH on ultrasound.Our study had several limitations. The sample size was small and lacked the ability to test the same number of residents and attendings per PGY level. Although using fresh frozen cadavers provided simulation of true pathology, the lack of eye movement seen in live patients may have allowed for easier detection of RBH. The cadaver models did not represent several other aspects of real-life diagnosis, such as patient discomfort, uncooperative patients, or concomitant traumatic injuries . Additionally, this cadaver model contained other ocular pathology on ultrasound, such as the appearance of retinal detachments (likely resulting from cadaver preparation). This study was also limited to the evaluation of RBH greater than 10 cubic centimeters in volume, and there is likely a decrease in sensitivity and specificity with smaller volumes. Future studies could assess the accuracy of identifying different retrobulbar volumes. Despite these limitations, this approach represents a feasible method for reliably representing a rare pathology for physician education.Emergency physicians can use POCUS to correctly identify a cadaveric model of RBH. Higher levels of training seem to correlate with improved accuracy in diagnosing this condition. Use of this model can improve clinicians’ exposure to the appearance of rare, vision-threatening ocular pathology, such as RBH. More study will be needed to assess the accuracy of POCUS for identifying retrobulbar hemorrhage in live patients.