Previous research suggests that the birth of a preterm child with very low birth weight  can be traumatic for both parents and lead to short-term consequences like clinical levels of posttraumatic stress symptoms (PTSS) or even to the development of a Posttraumatic Stress Disorder (PTSD). However, little is known about possible mid- and long-term psychological consequences in affected parents. The purpose of this study were (a) to examine the prevalence of parental birth-related PTSS and PTSD in a group of parents with VLBW preterm infants compared to parents of full-term infants 5 years after birth and (b) to investigate potential associations with risk factors for parental PTSS at 5 years postpartum. Perinatal factors , psychological factors  and sociodemographic characteristics , were included in the analysis. The sample consisted of 144 families  who participated in the prospective longitudinal cohort study “Hamburg study of VLBW and full-term infant development” (HaFEn-study) and were initially recruited at three perinatal care centers in Hamburg, Germany. PTSD prevalence and PTSS of mothers and fathers were assessed with the Impact of Event Scale-Revised (IES-R), social support with the Questionnaire of Social Support (SOZU-K-22), and lifetime psychiatric diagnoses with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID-I). Data were analyzed by hierarchic multiple regression analyses. Results showed that 5 years after birth none of the parents fulfilled the criteria for a birth-related PTSD diagnosis. For mothers, postnatal PTSS and a VLBW preterm birth significantly predicted PTSS 5 years postpartum. For fathers, psychiatric lifetime diagnosis and postnatal PTSS significantly predicted PTSS 5 years after birth. Early identification of parents with higher risk of PTSS, especially after VLBW preterm birth, and their clinical needs seems beneficial to reduce the risk of long-term consequences. More research is needed on the paternal perspective and on potential effects of preterm birth on both parents and their children's mental health outcomes. The birth of a child can be perceived as traumatic, if overwhelming feelings of helplessness, fear, loss of control and pain prevail . A pretePTSS as a response to a traumatic event can manifest in 4 main clusters (a) intrusion of unwanted trauma-related memories, (b) avoidance of trauma-related thoughts or external reminders, (c) negative alterations in cognitions and mood, and (d) alterations in hyperarousal and altered reactivity. The diagnostic criteria for a PTSD are fulfilled, if symptoms from each of these clusters are reported and persist for at least 1 month . ElevateIn general, the prevalences of parental PTSD and PTSS vary between studies due to different diagnostic criteria of the ICD-10, DSM-IV, and DSM-5, different assessment instruments, time points and samples. For mothers of moderate to late preterm infants, Mehler et al.  documentThere is some evidence on the persistence of PTSS in affected mothers. Lotterman et al.  reportedResearch on fathers is scarce, however, more studies in recent years have also included their perspective. Several studies showed higher PTSS for fathers of preterm children compared to fathers of term children , 17–19.For fathers of moderate to late preterm children, Mehler et al.  reportedStudies on the persistence of PTSS in fathers over time included shorter time periods compared to studies on mothers. Mehler et al.  describeAccording to the revised diathesis-stress model of the etiology of perinatal PTSD, there are birth-related risk factors, and also prenatal vulnerability factors and postpartum maintaining factors .The birth of a VLBW infant itself can be considered as an important risk factor for parental PTSS since the confrontation with the fragile and vulnerable baby and its potentially life-threatening condition, the exhausting time of hospitalization on the neonatal intensive care unit (NICU) and worries about possible health risks and prospective disabilities in the child are challenging aspects , 16, 23.Furthermore, perceived stress during birth is discussed as a crucial perinatal risk factor and was associated with parental PTSS 4–6 weeks postpartum . Two metOne important general risk factor is lack of social support, both during pregnancy, childbirth, and the postpartum transition into parenthood , 22. PerOne important prenatal vulnerability factor for postpartum PTSS is a lifetime diagnosis of a psychiatric disorder. The meta-analysis of Ayers et al.  demonstrOne important postpartum maintaining risk factor is high postnatal PTSS levels. One study described that mothers of VLBW infants had significantly higher PTSS over the course of 14 months postpartum compared to mothers of term infants . LefkowiAspects of the family and socio-economic environment might also be additional risk factors for PTSS. Evidence on parity is mixed; a meta-analysis found a significant small, positive effect of parity on postpartum maternal PTSD . Other sLiterature on socioeconomic status (SES) and its connection to parental PTSS is quite diverse due to different conceptualizations of the construct and local sampling particularities. Evidence on potential differences regarding factors contributing to SES between parents of VLBW infants and parents of term infants is mixed , 30, 34.The purpose of this study were twofold: (a) to examine the prevalence of parental birth-related PTSS and PTSD in a group of parents with VLBW preterm infants compared to parents of full-term infants 5 years after birth and (b) to investigate potential risk factors for parental PTSS 5 years postpartum: We expected the birth of a VLBW infant, higher perceived stress during birth, low perceived social support, a history of psychiatric diagnosis, and high postnatal PTSS levels to predict higher PTSS levels 5 years after birth.All data presented here stem from the prospective cohort study “Hamburg study of VLBW and full-term infant development” (HaFEn-Study), a multicenter longitudinal study from the greater Hamburg area in Germany. Families with VLBW preterm infants and families with term infants as control group were recruited between July 2006 and October 2008. The overall aim of the HaFEn-Study was to examine the association between parental mental health and child development. Questionnaires, clinical interviews, development testing, and assessment of parent-child-interaction were applied during 6 measurement points over 8 years . The study followed the Declaration of Helsinki and Good Clinical Practice Guidelines, and was approved by the Ethics Committee of the Chamber of Physicians in Hamburg, Germany.The recruitment of parents with singletons and multiples took place in the three largest perinatal medical care centers in Hamburg, Germany. The following inclusion criteria were applied for the VLBW preterm group : being born preterm (<37 weeks of gestation) and a birth weight of <1,500 g. Multiples were included when at least one infant was born with VLBW. All VLBW infants were born preterm. Inclusion criteria for the term group  were ≥37 weeks of gestation for singletons and ≥34 weeks for multiples. The following exclusion criteria were applied for the preterm and term group: insufficient language skills, inability to follow study procedures, premature discharge, residing too far from the study center, and infant death before the first assessment. Four to six weeks after the birth, while the child was treated in the NICU, parents were informed about the study and asked for their participation. As a control group, parents with full-term infants born in the participating centers were selected via file withdrawal, contacted within the first week after birth and also assessed at 4–6 weeks postpartum, if interested. The sample selection is depicted in X = −0.02 × intrusion score + 0.07 × avoidance score + 0.15 × hyperarousal score – 4.36  – 4.36  wasPsychiatric lifetime diagnoses  were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition SCID-I , 42]. Th. Th42)].Multiple pregnancy, the number of previous children and SES were assessed at study intake (T1) and included as control variables into the analysis. The SES was assessed with the German Winkler-Index  that comn = 109 cases were necessary to achieve a power of 80% (Gpower 3.1.9.2). Analyses were conducted with IBM SPSS 22.First, the sample characteristics and distribution of for maternal and paternal PTSS at T5 and the control and predictor variables were investigated based on descriptive statistics. Pearson correlations were calculated to investigate the bivariate association between the variables included for the main analysis. To investigate the research question, hierarchical multiple linear regression analyses with block-wise entry were conducted. In step 1, the main model was tested with the predictor variables multiple pregnancy and number of children, birth status and perceived stress during birth, perceived social support and psychiatric lifetime diagnosis. The control variable SES was entered in step 2, and finally PTSS at T1 as a last control variable at step 3. Analyses were conducted separately for mothers and fathers. Missing values in the predictor variables were replaced using Expectation–Maximization imputation . Regarding statistical power for the regression analysis, an expected minimum effect of medium size, at least n = 144 families , consisting of N = 139 mothers  and N = 104 fathers  are depicted in SD = 4.61; range = 20 to 45), whereas fathers had an average age of 35.3 years . Both the maternal and paternal sample had mostly an average to high SES at T1. Five years after birth (T5), most of the participants were married to or in a relationship with the biological parent of their child. Only a small number of parents were either divorced or single parent.Sociodemographic characteristics of the sample of n = 57 (74.0%) families had singletons, n = 19 (24.7%) had twins and n = 1 (1.3%) had triplets. This distribution was different from the term group, in which n = 59 (88.1%) families had a single child and n = 8 (11.9%) had twins. The birth mode also differed depending on birth status. In the preterm group, the majority of children  were delivered by a Cesarean section and n = 10 (13.0%) of the women gave birth vaginally. Women in the term group had fewer Cesarean sections  and more vaginal births . In the maternal sample, gestational age in the VLBW preterm group ranged from 23 to 33 weeks , compared to 34 to 42 weeks  in the term group. Birth weight ranged from 380 to 1,495 g , and from 1,795 to 4,555 g, respectively . In the paternal sample, gestational age ranged in the VLBW preterm group from 23 to 34 , compared to 34 to 42 weeks  in the control group. Birth weight ranged from 410 to 1,490 g, and from 1,795 to 4,300 g, respectively.Among the preterm group, SD of the IES-R scores were higher in mothers of preterm infants compared to mothers of term infants).In n = 37 (26.6%) of mothers and n = 9 (8.7%) of fathers fulfilled the diagnostic criteria , with birth status and perceived social support having significant, negative, and perceived stress during birth a significant, positive effect on PTSS at T5. At step 2, adding SES as a control variable did not significantly increase the amount of explained variance . However, the effect of perceived social support was no longer significant. Adding the control variable PTSS at T1 in the third and last step explained an additional 12% of variance in maternal PTSS at T5 . The effect of perceived stress during birth was no longer significant. Thus, birth status and PTSS level at T1 were the only significant predictors. Women who gave birth preterm and reported higher PTSS level at T1 also reported higher PTSS at T5.Results of the multiple regression analysis are listed in R2adj = 0.004, p = 0.469). Adding the control variable PTSS at T1 in the third and final step significantly explained an additional 21% of variance in PTSS at T5 , with a positive direction of effects. In this final model, the effects of multiple pregnancy and perceived stress during birth turned insignificant. Thus, fathers with a psychiatric lifetime diagnosis and higher PTSS at T1 reported significantly higher PTSS at T5.For fathers, a total of 43% of variance was predicted by the included variables. In the first step, the predictor variables explained 21% of variance in paternal PTSS at T5, with multiple pregnancy having a significant positive, and both perceived stress during birth and DSM lifetime diagnosis having a significant, negative effect on paternal PTSS at T5. Adding SES as a control variable into the model in the second step did not significantly explain additional variance in paternal PTSS at T5  = −2.36, p < 0.05. For fathers, a small difference was found for SES, with responders having a slightly higher SES than non-responders, t(223) = 2.34, p < 0.05. Significantly fewer responders fulfilled the criteria for a psychiatric lifetime diagnosis at T1 compared to non-responders, χ2(2) = 40.24, p < 0.01.Additionally, an analysis on differences between responders and non-responders at T5 was conducted see  in orderThis study aimed at examining the prevalence of parental birth-related PTSD and PTSS 5 years after the birth of a VLBW infant compared to parents of full-term infants and investigating potential risk factors for birth-related traumatic stress symptoms 5 years postpartum.Five years postpartum, none of the parents fulfilled the cut-off criteria indicating a PTSD diagnosis based on the calculated IES-R formula  and the For the mothers, one third of the variance was explained by the final model. Having a preterm VLBW infant and higher PTSS symptoms in the postnatal phase were significant risk factors for PTSS 5 years after birth for mothers. For the fathers, almost 43% of the variance was explained by the final model. Significant risk factors were a previous psychiatric lifetime diagnosis and higher PTSS symptoms shortly after birth. Interestingly, the birth status of their infant was not relevant for the fathers.As expected, the present study showed a moderate association between birth-related PTSS at 4–6 weeks postpartum and PTSS at 5 years postpartum for mothers and fathers. Compared to the other included predictor and control variables, PTSS at 4–6 weeks postpartum explained individually the highest amount of variance for maternal and paternal PTSS at 5 years postpartum. These associations demonstrate a relevance of PTSS up to 5 years after birth. Parental posttraumatic stress can affect the development of parent-child-relationships and child outcome. For example, mothers with more PTSS were less effective in structuring interactions with their preterm children . FurtherThe hypothesis on the association between lifetime diagnosis of mental disorder and PTSS 5 years after birth has been confirmed in our study for fathers. Literature shows that there are barriers for men for seeking psychological support , 49. ThiOne relatively general risk factor is the lack of social support . In our In contrast to recent findings and our hypothesis , 22, perOverall, average PTSS levels 5 years after birth were rather low in our sample; however, the level of PTSS varied more strongly for mothers with VLBW infants than mothers of term infants. The present study focused specifically on birth-related PTSS. It is well-documented that parents whose children were hospitalized due to preterm birth or other serious illness experienced high levels of parenting or parental stress during the time on the NICU –53 and sPTSS in the early postpartum phase were found to be predictive for PTSS 5 years after birth for both mothers and fathers. This certain persistence highlights the importance of early action. From a clinical perspective, screening of PTSS in both mothers and fathers of VLBW infants on the NICU is recommended , 17. If Our study has several limitations. First, the prevalence of PTSD was not assessed with a structured clinical interview but by applying a cut-off point on the IES-R. Second, the IES-R assesses PTSS according to the symptom clusters of the DSM-IV; thus, the fourth symptom cluster  introduced in the DSM-5 is not included in the present study. Third, the measurement of PTSS in postnatal women might be complicated due to some overlapping characteristics: some hyperarousal items assessed by the IES-R  are commonly endorsed by postnatal women shortly after birth independent of posttraumatic stress . Fourth,Our results show that the impact of potential risk and protective factors on the course of postpartum PTSS in parents of VLBW infants should be further investigated, taking also characteristics of the child into account. Additionally, there is a need for longitudinal analyses of trajectories of postpartum PTSS in both mothers and fathers of VLBW infants and over the course of several years. This would help to gain a better understanding of the development and relevance of PTSS beyond the time after birth.bindt@uke.de.The datasets presented in this article are not readily available because of the ethical committee's decision. Requests to access the datasets should be directed to The studies involving human participants were reviewed and approved by Ethics Committee of the Chamber of Physicians in Hamburg, Germany. The patients/participants provided their written informed consent to participate in this study.DB managed the literature searches, interpreted the results, and drafted the manuscript. AG organized the data management, designed and conducted the statistical data analysis, and interpreted the results. CBa designed and conducted the statistical data analysis. NH participated in performing the study by both collecting data and as supervisor and interpreted the results. CBi designed the study, participated in performing the study as supervisor, managed the literature searches, and drafted the manuscript. All authors significantly contributed to and have approved the final 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.


The purpose of this study was to investigate refraction at birth and during the first year of life in a large cohort of babies born in a single center in Northern Italy. We also aimed to analyze refractive errors in relation to the gestational age at birth. An observational ophthalmological assessment was performed within 24 h of birth on 12,427 newborns. Refraction was examined using streak retinoscopy after the administration of tropicamide (1%). Values in the range of between +0.50 ≤ D ≤ +4.00 were defined as physiological refraction at birth. Newborns with refraction values outside of the physiological range were followed up during the first year of life. Comparative analyses were conducted in a subgroup of babies with known gestational ages. The following distribution of refraction at birth was recorded: 88.03% of the babies had physiological refraction, 5.03% had moderate hyperopia, 2.14% had severe hyperopia, 3.4%, had emmetropia, 0.45%, had myopia, 0.94% had astigmatism, and 0.01% had anisometropia. By the end of the first year of life, we observed reductions in hyperopia and astigmatism, and stabilization of myopia. Preterm babies had a four-fold higher risk of congenital myopia and a three-fold higher risk of congenital emmetropia as compared to term babies. Refraction profiles obtained at birth changed during the first year of life, leading to a normalization of the refraction values. Gestational age at birth affected the incidence of refractive errors and amblyopia. Thus, the basic prerequisite for a good level of refraction and optimal visual functioning is regularity in ocular growth. However, there are convincing data showing that in the early developmental phase, good visual functioning plays a decisive role in establishing correct ocular growth . This deAbnormal refraction is the main risk factor for the development of amblyopia, which is the most common cause of visual impairment in children. Amblyopia leads to strabismus and a reduction in binocular vision. In addition, it may limit future employment opportunities and increase risk for psychosocial problems. It is a widely held clinical belief that the risk of developing amblyopia and strabismus can be reduced if abnormal refraction is promptly identified and corrected –9.A binocular disparity refers to the difference in the images of a single object seen by each eye, due the difference in angular position on the retina, and the inherent light disparity between each eye. This subtle disparity between retinal images is detected by the brain and provides important information about the depth structure of the world around us . The abiConsidering the importance of refraction in the development of amblyopia, we assessed the distribution of refraction in newborns and followed up babies considered to be at risk for future refractive-related ocular abnormalities for a period of 1 year. Moreover, we investigated the associations between refractive errors, gestational age (GA), and weight at birth in a cohort of 12,427 newborns.A collaborative observational study was conducted by the Departments of Ophthalmology and Neonatology of the University of Brescia, Italy, over a 5-year period. Ophthalmologic screening was performed on all newborns within 24 h of birth. Patient screening included spontaneous ocular motility examination, adnexa and anterior segment inspection, indirect fundus ophthalmoscopy, and cycloplegic retinoscopy. All children received one drop of proparacaine in each eye followed by one drop of tropicamide (1%) and then a second drop of tropicamide 5 min later. Streak retinoscopy was performed in a dimly lit room light with streak retinoscopy at least 20 min after the second tropicamide drop. Residual accommodation was excluded by taking several readings for each infant to assess variability in retinoscopy reflex. Findings were recorded after obtaining readings with no variations, as suggested by Varughese et al. .Hyperopia values between +0.5 D and +4.00 D were considered to be within physiological refraction at birth . NewbornComparative analyses were conducted in a subgroup of babies with known gestational age (GA). Newborns were classified as preterm if the delivery occurred before the 38th week of GA.2) and Kruskal–Wallis tests were used for statistical evaluations. Statistical significance was set at a p < 0.05.SPSS statistical software  was used for data analysis. Chi-square  were included in the study. The distribution of refraction at birth was as follows: 88.03% of the babies had physiological refraction, 5.03% had middle-high hyperopia, 2.14% had high hyperopia, 3.4% had emmetropia, 0.45% had congenital myopia, 0.94% had astigmatism , and 0.01% had anisometropia .The second outcome of our study was to investigate the association between the GA and refraction at birth. Data on the GA were collected for ~1 year in a subgroup of 3,600 newborns. Preterm infants constituted 11.3% of the babies with hyperopia , 30% of the babies with emmetropia, and 34% of the babies with myopia.2 = 70.1; p < 0.001, Kruskal–Wallis test). The odds ratio of congenital emmetropia in preterm babies was 3.31  . The odds ratio of congenital myopia in preterm babies was 4.03   . The mea.1–7.48) .We also analyzed the development of refractive errors during the first year of life  and 4. TMyopia developed in 5% of the babies with hyperopia, whereas no further worsening of myopia was recorded. At the end of the follow-up period, seven patients with myopia (50%) continued to have myopia, whereas six patients developed mild hyperopia or emmetropia. Moreover, six patients who previously had hyperopia or astigmatism developed myopia. At the end of follow-up, the total number of babies with myopia remained constant . Only seThe aim of this study was to investigate the distribution of refraction at birth in a large cohort of babies and analyze its association with the GA. Changes in refraction during the first year of life in a subgroup of babies diagnosed with a pathological condition at birth were also evaluated.Physiological hyperopia and non-physiological refraction were observed in 78% and 22% of the newborns, respectively. Refraction was classified as pathological or physiological according to the adopted classification: hyperopia up to +4.00 D was considered physiological at birth, as was hyperopia up to +3.50 D at 8 months  and up tA coordinated development in both corneal power and in axial length modifies the distribution of spherical equivalent refraction from an uniform to a highly peaked hyperopic distribution , 19. It In this study, astigmatism resolved spontaneously in the first year of life in almost all cases. This resolution occurs because of a physiological decrease in the toricity of the cornea and anterior lens, combined with a decrease in the variability of corneal lenticular surfaces. However, persistent infantile astigmatism is associated with increased astigmatism and myopia during school years –33. In tAnisometropia was found in a very limited number of babies. It has been suggested that anisometropia at birth can resolve spontaneously over time. However, according to Almeder et al.  and to DAccommodation in children is very powerful, and consequently, it is important to reach a healthly level of cycloplegia before retinoscopy. To reduce the risk of adverse reactions associated with atropine or cyclopentolate, we decided to use tropicamide (1%). However, as Mutti et al. found, when the drops are properly administered, the degree of difference between cyclopentolate and tropicamide is quite small, and there is a minimal effect on the measurement of distance refractive error and ocular optical components –39. We aAlthough cyclopentolate 0.5% is a better cycloplegic agent than tropicamide (1%) and has been used in other studies , it alsoOther reasons responsible for the low number of anisometropia patients could be the use of a higher cut-off  values compared with other published studies.Another interesting aspect of our study is the analysis of refractive errors in relation to GA in preterm and term babies. In particular, preterm babies were found to have a higher risk for congenital myopia and emmetropia, as compared to babies born at term. This is in agreement with previous studies , 42–44. In this study, we observed a reduction of hyperopia and astigmatism, and stabilization of myopia by the first year of life. Preterm babies had a four-fold higher risk of developing congenital myopia and a three-fold higher risk of developing congenital emmetropia, as compared to term babies.We also found that refractive distribution obtained at birth changed during the first year of life, leading to a normalization of the refraction values, and that gestational age at birth affected the incidence of refractive errors and amblyopia. The strengths of this study was the large number of children analyzed. Its limitation was the lack of follow- up for babies with physiological hyperopia.In conclusion, ophthalmic screening in preterm babies is primarily useful to identify potentially blinding pathologies , although this is difficult to diagnose in very young infants, particularly by non-eye doctors. The adoption of a screening protocol at birth is associated with a lower prevalence of amblyopia by scholar age, which allows sufficient time for early treatment of amblyopia .Overall, the data collected in our study provide useful insight for understanding refraction in newborns.All datasets generated for this study are included in the article/supplementary material.The study has been reviewed and approved by the Ethics Committee of Spedali Civili di Brescia. The study was performed in accordance with the principles of the Declaration of Helsinki and received the approval by the Institutional Review Board. Parental written consent was obtained for all participants, before inclusion in the study.EF and GN performed data collection, writing, editing. SC, VB, MF, and SB contributed to data acquisition, review and editing, statistical analyses. FS and CC contributed to all facets of the work, and edited 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.


Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants.A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO  or saline  intravenously within 72 h of birth and then once every other day for 2 weeks.. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group . Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys  and in those with a gestational age of 28–296/7 weeks  and birth weight of 1000–1499 g . There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment.The total incidence of ROP was not significantly different between the two groups  on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500. Anaemia of prematurity is common in preterm infants, especially in very preterm infants born at < 32 weeks of gestation . It is cROP is a proliferative retinal vascular disease affecting the retina of premature infants, and is characterised by neovascularisation, secondary to peripheral retinal ischemia, and subsequent neuro-vascular degeneration . The cliHowever, the effect of rhEPO administration on the development of ROP in preterm infants is still unclear. Vitreous levels of EPO are elevated in preterm infants who developed neovascularisation during phase 2 of ROP . Moreove6/7 weeks, and 30–32 weeks) in NICUs . Accordingly, transfusion requirements were much lower in the rhEPO group (1.5 ± 1.7) than in the control group:   × 10 × 1012/LOverall, rhEPO was well tolerated in the current treatment protocol. In very preterm infants, there were no differences between the rhEPO and control groups in liver and renal functions or in electrolyte levels (data not shown). In addition, no adverse effects, including allergic reactions, venous thromboses, rashes, or seizures, were observed in either the rhEPO or the control group.6/7 weeks and with a birth weight between 1000 and 1499 g.In these randomized trials reanalysis, we found that the effect of early administration of rhEPO on ROP in very preterm infants is associated with the gestation age, birth weight. Overall, low dose rhEPO treatment did not have an impact on the incidence of ROP development in very preterm infants. Rather, it was associated with a reduced risk of ROP in some groups of preterm infants. The incidence of type 2 ROP was reduced in infants with a gestational age between 28 and 30 weeks and bodyweight of 1000–1499 g compared to the control group. The administration of low dose rhEPO also reduced the incidence of type 2 ROP in infants with a gestational age between 28 and 29To note, in infants with a gestational age of < 28 weeks and with a birth weight of < 1000 g, there was a non-significant increased incidence of ROP. This may indicate that the effect of EPO on ROP in preterm infants might be gestational age- and birth weight-dependent. In this subgroup of infants with a gestational age of < 28 weeks, we only have 76 infants in the rhEPO treatment group and 71 in the control group, and infants with birth weight < 1000 g, we only have 73 in the rhEPO treatment group and 74 in the control group. Considering the small number of ROP, the results from the current study for this group of infants is not conclusive. Indeed, in the most recently closed Preterm Erythropoietin Neuroprotection Trial (PENUT) for assessing the safety and efficacy of early high-dose erythropoietin for neuroprotection in extremely preterm infants, they found that in contrast to previous meta-analyses, treatment with rhEPO did not result in a higher rate or greater severity of retinopathy of prematurity than placebo .In the subgroup analysis, rhEPO led to a decrease in the rate of type 2 ROP in infant boys but not in infant girls, suggesting a sex-differential response to rhEPO. It has been reported that the overall production of EPO is suppressed by oestrogen in rodents under normoxic or hypoxic conditions . This fiAnaemia of prematurity is a common condition in preterm infants, particularly in extremely preterm infants, born before 28 weeks of gestation , 36. EarThere were some limitations to the current study. First, EPO concentration was not measured longitudinally, even though this had been performed in our first rhEPO clinical studies  . TherefoThe observational analysis retrieved from our previous prospective randomised clinical trial data found that early repeated low-dose administration of rhEPO is safe for very preterm infants and reduced the need for red blood cell transfusions, but no significant effect on the overall incidence of ROP, even though the gestation age- and birth weight-dependent effect of rhEPO administration on ROP in preterm infants has been noticed. However, considering the overall relatively low incidence of ROP among preterm infants, data from more large-scale clinical studies are needed to derive more conclusive results regarding rhEPO administration in very preterm infants.


GOT1 has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with GOT1 expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemotherapy alone, while 71 received allogeneic hematopoietic stem cell transplantation . In both treatment groups, high GOT1 expression was associated with shorter event-free survival (EFS) and overall survival (OS) . Multivariate analysis identified several independent risk factors for both EFS and OS in the chemotherapy-only group, including high GOT1 expression, age ≥60 years, white blood cell count ≥15 × 109/L, bone marrow blasts ≥70%, and DNMT3A, RUNX1 or TP53 mutations ; but in the allo-HSCT group, the only independent risk factor for survival was high GOT1 expression (P < 0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to GOT1 expression were mainly concentrated in “hematopoietic cell lineage” and “leukocyte transendothelial migration” signaling pathways. Collectively, GOT1 expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT.One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of  FLT3-ITD, NPM1, CEBPA, RUNX1, TP53, and ASXL1 mutations (sFRP2) and docking protein 7 (DOK7) genes are associated with better outcome , the most common type of acute leukemia, is a clinically, genetically, and molecularly heterogeneous disease associated with uncontrolled proliferation and blocked differentiation of immature myeloid progenitors . The choutations . Additioutations . For exa outcome , while hKRAS mutant CRC cells with GOT1 promotes proliferation and reduces apoptosis, suggesting that GOT1 is required for cell survival , a curative treatment for AML  were screened for patients with GOT1 expression data and a total of 155 AML patients were included in this study  white blood cell count (WBC), PB and bone marrow (BM) blast percentage, French-American-British (FAB) subtypes, and the frequencies of known recurrent genetic mutations. Primary endpoints were event-free survival (EFS) and overall survival (OS). The former was defined as the time from diagnosis to the first event including relapse, death, failure to achieve complete remission, or was censored at the last follow up. The latter was the time from diagnosis to death from any cause, or was censored at the last follow-up.The Cancer Genome Atlas (TCGA) database . Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted to evaluate the enrichment of GOT1-related gene expressions. A two-tailed P < 0.05 was considered statistically significant. All statistical analyses were performed by the SPSS software 22.0, the R software 3.5.0, and the GraphPad Prism software 7.0.Descriptive statistics were used to summarize patients' clinical and molecular characteristics by median and/or range. Due to the non-normal distribution of the numerical data, a nonparametric test, i.e., the Wilcoxon-Mann-Whitney test, was used for between-group comparison. The chi-square test was used for between-group comparison of categorical data. Survival was estimated using the Kaplan-Meier methods and log-rank test. For multivariate analysis of EFS and OS, Cox proportional hazard models were constructed, using a limited backward elimination procedure. Spearman correlation analysis was used to determine the relationships between GOT1 expression levels. Within each group, the comparison of clinical and molecular characteristics between high and low GOT1 expression subgroups were summarized in The chemotherapy-only and the allo-HSCT groups were each divided in two by the respective median GOT1high subgroup had fewer patients with CBFβ-MYH11 (P = 0.026) and RUNX1 mutations (P = 0.019), but more with MLL fusions (P = 0.004), FLT3-ITD and NPM1 mutations , than the GOT1low subgroup. Age, gender distribution, WBC count, BM/PB blast percentage, FAB subtype distribution, risk stratification, frequencies of other recurrent genetic mutations , as well as the relapse rates, were similar in the two subgroups.In the chemotherapy-only group, the P = 0.001), intermediate-risk (P = 0.007), FLT3-ITD and NPM1 mutations  were more common in the GOT1high subgroup, but CBFβ-MYH11 (P = 0.054) and good-risk (P = 0.011) were less in the GOT1high subgroup. They also had higher relapse rate than the GOT1low subgroup. Age, gender distribution, WBC count, BM/PB blast percentage, FAB distribution, and frequencies of other recurrent genetic mutations , were similar in the two groups.In the allo-HSCT group, normal karyotype  and other commonly utilized AML risk stratification indices were used to construct multivariate analyses. The later included age (≥60 vs. <60 years), WBC count (≥15 vs. <15 × 109/L), BM blast percentage (≥70 vs. <70%), PB blast percentage (≥20 vs. <20%), FLT3-ITD (positive vs. negative), and other common genetic mutations .To further assess the prognostic value of GOT1 expression, older age, higher WBC count and BM blast percentage, and mutations in DNMT3A, RUNX1, and TP53, were independent risk factors for both EFS and OS .In the chemotherapy-only group , high GOGOT1 expression was also an independent risk factor for both EFS and OS . For EFS, other independent risk factors included higher WBC count, FLT3-ITD and NPM1 mutations ; RUNX1 and TP53 mutations were independent risk factors for OS .In the allo-HSCT group , high GOGOT1 on AML, the high throughput sequencing information from TCGA database was used to summarize the GOT1-related gene expression profile. Three hundred and thirty-six up-regulated and 842 down-regulated genes that were significantly associated with GOT1 expression , thus reprogramming glutamine metabolism  involved in “cytokine-cytokine receptor interaction”, “osteoclast differentiation”, “chemokine signaling pathway”, “hematopoietic cell lineage”, and “leukocyte transendothelial migration” signaling pathways are significantly correlated with the GOT1 expression. It could be deduced that GOT1 might be involved in leukemogenesis through aforesaid pathways, although this would require further studies to confirm.The tumorigenesis role of tabolism . Furtherl growth . This mel growth . We foun9/L also independently contribute to poor survival. This is concordant with older studies that older age confers unfavorable prognosis in AML, possibly due to higher mutation burden, lower baseline performance status and more co-morbidities in this population . We were not involved direct interaction with patients. All analyses during this study were included in this article.All data in this study were publicly accessible from The Cancer Genome Atlas (TCGA) database (ZC and LF conceived the study and wrote the manuscript. YD and TZ collected and analyzed the data. YL, LC, TQ, CS, WH, YP, XY, and JS participated in analyzing and discussing the results. All authors edited and approved the final 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.


However, in their assessment, Devakumar and colleagues ignore the significant benefits shown in the individual patient data (IPD) meta-analysis, which strongly influenced our task force’s conclusions. Rather, their comments focus only on the birth size data from the Cochrane reviews.3 In the IPD meta-analysis, which included data from nearly 113,000 pregnancies, the authors found that, in addition to reducing the risk of low birthweight, MMS significantly reduces the risk of preterm birth (RR = 0.93 (0.87–0.98), random effects).2 The Cochrane review also states that MMS “probably led to as light reduction in preterm births” on the basis of data from 91,425 participants with moderate quality evidence (RR = 0.95 (0.90–1.01)).3We appreciate the comments by Devakumar Cochrane review only used the latter. In the IPD meta-analysis, the authors found that MMS (compared with iron and folic acid supplementation) significantly reduced neonatal mortality among female infants (RR = 0.85 (0.75–0.96)), and had similar significant effects on 6-month and infant mortality, with no effect among males, and reduced 6-month mortality (RR = 0.71 (0.60–0.86)) among all infants born to anemic mothers.2 The subgroup analyses also showed that the benefit of MMS with regard to reducing the risk of preterm birth (RR = 0.84 (0.78–0.91)) was greater among infants born to under-weight mothers than among those born to women who were not underweight. The global prevalence estimates of underweight (>200 million women of reproductive age)4 and anemia (>528 million women of reproductive age)5 are very high, and prevalence rates are highest in low- and middle-income countries, where these MMS trials took place. Thus, in such settings, MMS is likely to benefit a substantial proportion of infants. The potential benefits of MMS for women who are depleted in nutrients other than iron and folate also merit further exploration.One of the greatest strengths of an IPD meta-analysis is the ability to include predefined subgroup analyses that are based on the individual data, rather than trial-level aggregate data. The meta-analysis in the 6 Reducing low birthweight rates remains a World Health Assembly target, and interventions that can reduce the risk of low birthweight, such as MMS, should be encouraged.In addition to the short-term benefits of MMS with regard to birth outcomes, the likely longer term consequences of reducing low birthweight and preterm birth should be considered. Low birthweight infants are at an increased risk of death not just during infancy but throughout life, and low birthweight is also associated with reduced lung capacity and immune function as well as an increase in certain cancers.et al. standard aggregated data meta-analysis includes mortality and anthropometric data for follow-up periods ranging from 6 months to 9 years after birth and combines studies that did and did not continue nutritional interventions after birth, making direct comparisons across studies difficult.7 Moreover, there is a risk of bias in the existing evidence from follow-up studies because of loss to follow up due to mortality. Valid and reliable cognitive assessments in very young children remain a challenge, which reduces the likelihood of detecting intervention group differences; a much wider array of assessments can be conducted among older children and adults. Recent results on adolescent cognition from a study in rural Western China are encouraging .8 In that study, which included more than 2,100 14-year olds, the investigators found that children whose mothers received MMS during pregnancy had a dose-dependent improvement in intellectual development. The findings of that study are similar to those of the follow-up study of school-age children in the Indonesian SUMMIT study at 9–12 years of age.9More information would be useful regarding the long-term benefits or consequences of all prenatal interventions. For MMS, the evidence continues to accrue from long-term follow-up of trial participants. We note that the Devakumar Cochrane review and the IPD meta-analysis, the task force is of the opinion that there is sufficient evidence to inform policy decisions now, without waiting for more evidence on long-term outcomes. We agree with Devakumar et al. that improving health outcomes through nutrition interventions requires a life-course approach. MMS is just one intervention during one phase of the life course, and pregnant women in food-insecure situations may need improved macro- as well as micronutrient intake. That said, in populations at risk, MMS during pregnancy can allow infants to begin life with a significant advantage.On the basis of the evidence provided by the


Uterus didelphys is a rare form of congenital anomaly of the Müllerian ducts. The clinical significance of this anomaly of the female reproductive tract is associated with various reproductive issues: increased risk of preterm birth before 37 weeks’ gestation, abnormal fetal presentation, delivery by caesarean section, intrauterine fetal growth restriction, low birth weight less than 2500 g, and perinatal mortality. We present three cases of uterus didelphys and full-term pregnancy, which resulted in favorable birth outcomes of live-born, full-term infants. In two of the cases, delivery was performed via Caesarean section: due to lack of labor activity in one of the cases and lack of response to oxytocin stimulation in the second case. The weight of two of the new-born infants was lower than expected for the gestational age. Congenital anomalies of the female reproductive tract are of special interest because of their association with various reproductive difficulties: impaired possibility of natural or assisted conception, increased rate of first and second trimester miscarriages, preterm birth, placental abruption, lower birth weight and fetal growth restriction, malpresentation at delivery, and perinatal mortality . The preThe ASRM classification defines uterus didelphys, or didelphic uterus, as a reproductive tract anomaly representing a complete duplication of the uterus and cervix. It occurs as a result of a failure of Müllerian duct fusion in 8 weeks’ gestation ,7 The ESGenerally, this anomaly is presented by two uterine cervixes and two uteri, each linked to a fallopian tube. A longitudinal vaginal septum is present in 75% of the cases. Duplication in other organs-vulva, bladder, urethra, and anus may also be observed [We present three cases of the anomaly uterus didelphys at a full-term pregnancy and the difficulties faced in our attempt to achieve normal delivery.A 21 year-old patient was diagnosed with uterus didelphys anomaly one year earlier in the course of an undeveloped twin pregnancy in each uterine cavity. A residual abrasion was performed separately for both uteri at 8 weeks’ gestation. During her second pregnancy follow-up, the fetal estimated weight obtained by ultrasonography at 37 weeks was 2951g (between 50th–75th centile) [There was no dilatation of the right cervix, the left cervix was dilated to 2 cm with clear amniotic fluid leakage, and a Bishop score of 4 points  . ExternaA live-born infant weighing 2580 g, height 48 cm, and with an Apgar score of 9–10 points was delivered. The patient postpartum time period was uncomplicated. On the follow-up visit between 4–6 weeks, the patient was in good health condition and without complains.A 25 year-old first-time pregnant woman was admitted to the maternity ward 6 days after the likely probable expected date of delivery with an intact amniotic membrane and no labor activity. Uterus didelphys anomaly was diagnosed using 2D ultrasound examination on an outpatient basis during a female consultation visit. After spontaneous conception, ultrasonography at 8 weeks of gestations was performed .The fetal estimated weight obtained by ultrasonography during patient pregnancy consultation at 37 weeks was 3143 g (between 50th–75th centile) . The fetA 27 year-old patient at the 38th week of her third pregnancy, with initial labor activity, cardiotocographically verified contractions 5 min apart. The patient’s first pregnancy had ended as a spontaneous abortion at the 7th week. Her second pregnancy outcome was a normal delivery to a live-born infant weighing 3000 g. During her third pregnancy follow-up, the fetal estimated weight obtained by ultrasonography at 36 weeks was 2713 g (between 25th–50th centile) [Uterus didelphys is a rare anomaly and accounts for 8% of the congenital anomalies of the female reproductive tract . It occuThe ability to conceive is not typically impaired, but pregnancy in uterus didelphys is often associated with reproductive failure. A meta-analysis of 25 studies involving more than 160,000 women, of which 3766 with congenital uterine anomalies, shows that uterus didelphys was not associated with decreased natural or assisted fertility and an increased frequency of spontaneous abortions. The research establishes an increased risk of preterm birth before 37 weeks’ gestation, breech presentation, intrauterine growth retardation in the fetus, low birth weight infants of less than 2500 g, and perinatal death [Concerning the presented clinical cases, feto-pelvic-incompatibility and fetal asphyxia were excluded in all three patients, thus proceeding to a normal delivery. The administration of oxytocin stimulation or oxytocin induction was required in all three patients, as the inadequate response of uterine contractions was observed. In the first case, labor stimulation led to irregular and weak uterine contractions. In the second case, induction was unsuccessful. With both patients we proceeded with a surgical delivery. In the third patient, medications administered stimulation resulted in a normal childbirth but with a protracted first period. More than 80% of the pregnancies and childbirths in women with uterus didelphys end with a caesarean section but without immediate indication for it, research literature shows . VaginalOn the basis of our review of the literature, we think that CS and uterus didelphys is a sufficient, but not absolute indication for CS. However, although uterus didelphys and normal deliveries have been reported even after CS, we believe that surgical delivery is a safer method for this Müllerian anomaly . A more Congenital Müllerian anomalies are challenging case scenarios for obstetrician-gynecologists in terms of diagnosis and resolution of reproductive problems. Women with uterine anomalies are more likely to experience adverse pregnancy outcomes, which requires accurate knowledge, early diagnosis, and adequate treatment.


Finding orthologs remains an important bottleneck in comparative genomics analyses. While the authors of software for the quick comparison of protein sequences evaluate the speed of their software and compare their results against the most usual software for the task, it is not common for them to evaluate their software for more particular uses, such as finding orthologs as reciprocal best hits (RBH). Here we compared RBH results obtained using software that runs faster than blastp. Namely, lastal, diamond, and MMseqs2.We found that lastal required the least time to produce results. However, it yielded fewer results than any other program when comparing the proteins encoded by evolutionarily distant genomes. The program producing the most similar number of RBH to blastp was diamond ran with the “ultra-sensitive” option. However, this option was diamond’s slowest, with the “very-sensitive” option offering the best balance between speed and RBH results. The speeding up of the programs was much more evident when dealing with eukaryotic genomes, which code for more numerous proteins. For example, lastal took a median of approx. 1.5% of the blastp time to run with bacterial proteomes and 0.6% with eukaryotic ones, while diamond with the very-sensitive option took 7.4% and 5.2%, respectively. Though estimated error rates were very similar among the RBH obtained with all programs, RBH obtained with MMseqs2 had the lowest error rates among the programs tested.The fast algorithms for pairwise protein comparison produced results very similar to blast in a fraction of the time, with diamond offering the best compromise in speed, sensitivity and quality, as long as a sensitivity option, other than the default, was chosen. Finding orthologs is an important step in comparative genomics and represents a central concept in evolution. Orthologs are defined as characters that diverge after a speciation event . This noEfforts in standardizing methods for the inference of orthology remain in constant evaluation, with over forty web services available to the community , 7. Few v.g. ).The results above suggest that diamond, ran with the very-sensitive option, might be the best alternative to obtain RBH in terms of speed, sensitivity and quality. Our results also showed that the faster programs produced results with very similar error rate estimates as blastp. Improvements in speed were much more evident for the large databases involving eukaryotic proteomes.Escherichia coli K-12 MG1655 (RefSeq assembly id: GCF_000005845), and Bacillus subtilis 168 (GCF_000009045); as well as the eukaryotes Saccharomyces cerevisiae S288C (GCF_000146045) and Mus musculus (GCF_000001635).For these tests we used the sets of annotated protein sequences, or proteomes, from four reference genomes: the bacteria δ-distance cutoff of 0.04 as described previously [To compare against bacterial references, we used the annotated protein sequences of 3,312 non-redundant prokaryotic genomes. These non-redundant representatives were selected from approximately 16,000 complete prokaryotic genomes available at NCBI’s refSeq genome database  by Januaeviously , resultiMus musculus, proteome was reduced from 84,985 to 21,905 representative proteins.For the comparisons involving eukaryotes, we chose 78 genomes, each selected to represent the members of each eukaryotic taxonomic class with genomes available at the RefSeq database by July 2020. Since eukaryotic genomes often have more than one protein annotated per gene, mostly to account for alternative splicing, we cleaned up the eukaryotic proteomes by writing an ad hoc program to leave only one protein per gene. This way, for example, the mouse, Four programs were used to perform protein sequence comparisons: (1) blastp version 2.10.0+ , (2) lasTo compare times, each pairwise comparisons was run in the same computer, with no other programs running at the same time. Times were obtained by using the unix “time” command. This command reports user, cpu and real times. The plotted times were the real times. The computer was a six-core 2019 Mac mini with 64 GB of RAM. All programs were run to use four of the six available cpu threads in the machine.−6 (1e-6), coverage of 60% of the shortest protein in the alignment, as well as soft-masking and Smith-Waterman alignment, when available . The latter two options were previously found to improve the finding and quality of RBH with blastp [To find Reciprocal Best Hits (RBH), we wrote a wrap-up program, getRBH.pl , to stanh blastp .All four programs can work with their own target databases . These databases make the sequences easier to access and analyze, for example, by reducing the sequence alphabet, indexing for quick retrieval, sometimes precomputing “seeds” , or any other formatting for the efficient use of the respective sequence comparison programs. These databases are built using a program within the suite: “makeblastdb” for blastp, “lastdb” for lastal; or by a command within the program: “diamond makedb” for diamond, “mmseqs createdb” for mmseqs. We built databases for all programs .GSS) were calculated from blastp results as the sum of the bit scores of all reciprocal best hits (compScore) divided by the bit scores of the respective orthologs against themselves (selfScore). This calculation corresponds to the GSSa described in [Genomic Similarity Scores , where P is the number of paralog pairs found where an orthologous one was expected [The estimate of error rates relied on conservation of gene order. Ideally, if two adjacent genes, rthologs . In suchexpected .To show the intersection sizes between compared RBH datasets, in lieu of Venn/Euler diagrams, which are hard to draw and interpret when more than three sets are involved, we built matrix-based layouts using UpSetR v1.4.0  for R v.Additional file 1 Supplementary Figures.


To increase knowledge and promote cultural change toward valuing normal birth, and to lower rates of cesarean and unnecessary interventions during childbirth in Brazil via the Senses of Birth (SoB) exhibition.The SoB intervention targeted 22 621 participants in three Brazilian cities in 2015. The effects of the exhibition in knowledge, perceptions, and preferences regarding childbirth were analyzed in a multi-method study. Pre- and post-exhibition survey responses of 17 501 (77.0%) visitors, 1947 (8.6%) non-pregnant women, and all pregnant women (n=1287) were collected at the exhibition. A follow-up survey was completed by 555 (43.0%) postpartum women who had participated at SoB while pregnant. Univariate analyses were used to compare before and after changes.P<0.001) and 27.3% to 42.0% among pregnant women (P<0.001). Perceptions and preferences for normal birth also changed, reaching 83.0% of general visitors and 87.4% of pregnant women.There was a significant increase in knowledge about normal birth, varying from 10.0% to 25.0% among general visitors (SoB was found to effectively improve knowledge about and preference for normal birth. Scaling-up the intervention might contribute to cultural change toward valuing normal birth, and might decrease the rate of unnecessary cesarean and premature birth in Brazil. Many historic, ethical, political, economic, and sociocultural relationships have had an impact, and have resulted in the institutionalization of childbirth, such that 98% of childbirth occurs in a hospital.4 Furthermore, commercialization and medicalization of life, power relations in science, medicine, and gender, and the social representation of cesarean delivery as safe, fast, convenient, clean, and a painless procedure have contributed to the rise in cesarean delivery.4The rate of cesarean delivery in Brazil has been increasing for the past 40 years, reaching 57% in 2014.6 The most recent UN agenda, Sustainable Development Goals,7 calls for increased accountability by challenging health systems to identify and fight the preventable maternal and neonatal morbidity and mortality associated with the inadequate access to services, or “too little, too late”.9 It also questions the opposite extreme reality, “too much, too soon,” which may be associated with overmedicalization of normal prenatal, intrapartum, and postnatal care.9Different interventions are necessary to address this problem. The WHO has published best practice recommendations on childbirth care to improve rates of normal birth, and recently suggested that 15% should be the reference rate for cesarean delivery.10 and social movement initiatives have attempted to reverse this situation, with campaigns and social mobilization for the humanization of childbirth. However, cultural change cannot rely solely on norms of procedures and information campaigns; it also requires educational actions that promote critical thinking.Public policies11 The intervention was designed to support cultural transformation toward normalizing vaginal birth. To appraise the potential cultural transformation of this intervention, the aim of the present study was to analyze the effects SoB on the knowledge, perception, and preferences of visitors to the exhibition about normal birth and other aspects related to childbirth care.To contribute to cultural change to value normal birth, and reduce unnecessary interventions during childbirth, the Senses of Birth exhibition was structured as a cultural intervention and health education action to promote the debate and diffusion of evidence-based practices in childbirth and birth care.The present cross-sectional quantitative multi-centered study analyzed survey data collected through the Senses of Birth project during the exhibition in three Brazilian cities  from March 1 to August 31, 2015. The study was part of the research project named “Senses of Birth: effects of the interactive exhibition in the perception changes on labor and childbirth,” approved by the Federal University at Minas Gerais IRB . All participants provided informed consent through a signed consent form.Senses of Birth is an interactive exhibit that combines different languages  and media  to engage and excite the visitor and promote critical thinking. The free exhibition was open to the public and set-up in five Brazilian cities , receiving 42 170 visitors from March 1, 2015, to December 31, 2017.12 for a video presentation). It begins with the visitor being “impregnated” with a full term baby image projected in the visitor’s belly. A birth plan is then given to the new pregnant person  as a tool to inform and promote critical thinking about good practices and enabling them to plan their childbirth delivery. The “pregnant visitor” is then directed to the “convenience store”, where a vendor tries to sell labor and childbirth products, ironically disclosing childbirth business interests such as “Mama Beauty Spa” and a kit for planned cesarean delivery.The exhibition consists of five sections and a 40-minute interactive circuit .The second study population comprised visitors who answered a structured questionnaire before and after visiting the exhibition to measure changes in knowledge, perception, and preferences about normal vaginal birth. The group was selected by random sampling of 20% of the visiting population aged 18 years or older who agreed to participate; the sample size assumed a prevalence of 50% for the outcome , with a β level of 5%.The third study population comprised all pregnant women who visited the intervention and answered a specific self-administered questionnaire after experiencing the SoB intervention. The fourth study population comprised women who had participated at the SoB intervention during pregnancy and answered an online self-administered follow-up questionnaire after childbirth, collecting information about the birth process, utilization of good practices, and outcomes.14 The demographic information collected included sex, age, marital status, race (self-reported), family income , education level, and health insurance type. Healthcare variables included self-reported knowledge about normal birth, doula support, midwife care, the right to a companion during childbirth, non-pharmacologic methods for pain relief, rates of cesarean in Brazil, WHO and Ministry of Health recommendations on childbirth, obstetric violence, and birth plan. Additional healthcare variables included perceptions and feelings associated with childbirth, including fear, suffering, safety, and risks; preferences in childbirth, including normal birth and cesarean; and perceived ability to have a normal birth. For postpartum women, healthcare variables included use of a birth plan, midwife care during childbirth, doula care during childbirth, type of hospital during childbirth, type of birth, and gestational age at birth.The study variables were chosen on basis of the theory of planned behavior.χ2 test was used to compare outcomes before and after the SoB intervention; a P value of 0.05 was considered to be statistically significant.SPSS version 20  was used for statistical analysis. Variables were described by number (percentage) and stratified by the different study populations. Touch-screen data on before and after opinions about normal birth were assessed by κ statistics. The Pearson During the data-collection period, 22 621 visitors attended the SoB intervention and 17 501 (77.9%) provided touch-screen answers, which showed a substantial change in opinion about normal birth before and after visiting SoB. The percentage of people that reported their perception of normal birth as “terrible” , “bad” , or “no opinion”  decreased from 22.9% (n=4008) to 3.7% (n=641). The assessment of normal birth as “excellent” rose from 42.0% (n=7344) before to 81.4% (n=14 250) after the intervention .During the SoB, 1947 (8.6%) of the 17 501 visitors were interviewed: 1010 (51.9%) before and 937 (48.1%) after experiencing the intervention . The genAmong 1287 pregnant women visitors, the majority were self-reported black , married , and aged 20–34 years . Most had studied more than 12 years , and 959 (74.6%) were covered by private health insurance. A total of 517 (43.9%) women had a family income of more than five times the Brazilian minimum wage. The sample of postpartum women had characteristics similar to those of the pregnant women.In terms of the visitors’ perceived knowledge about subjects related to childbirth, there were significant changes before and after the intervention among all three study groups . The incConcerning perceptions and feelings before and after the SoB intervention, respectively, the visitors indicated that vaginal birth was associated with happiness, personal fulfillment, safety, confidence, and strength, but negatively associated with fear, pain, suffering, and risk. The percentage of visitors who associated anxiety with normal birth decreased after participating at SoB .After the intervention, 586 (65.6%) general visitors reported that they had changed their perception of normal birth, and 551 (61.0%) had changed their perception of cesarean delivery. Before participating, 780 (79.3%) visitors reported that they probably or definitely preferred normal birth; this proportion changed to 770 (83.3%) after the intervention (P=0.027). Similarly, 14.7% (n=143) participants reported that they preferred cesarean delivery before the SoB, and this proportion decreased to 10.4% (n=96) after the intervention (P<0.05). Most visitors  reported that they could have a vaginal birth before visiting SoB; this proportion increased after the intervention . Among pregnant women, 61.8% (n=770) changed their opinion about normal birth; 87.4% (n=1125) declared a preference for vaginal birth after the intervention and 90.2% (n=1137) considered themselves able to have a normal birth after the intervention. The findings were similar among postpartum women .Among the 555 (43.1%) postpartum women who completed the follow-up survey, 354 (63.9%) reported that they delivered at a private hospital. In total, 255 (45.9%) had a cesarean delivery, 151 (59.7%) of them before labor. Notably, they reported use of a birth plan , midwife care during labor , and/or doula support . Overall, 330 (76.7%) had access to non-pharmacologic birth pain relief methods, 70 (13.2%) reported obstetric violence in childbirth, and 41 (7.4%) gave birth prematurely .The SoB educational intervention contributed to improvement in self-reported knowledge, as well as a change in perception and preferences about normal birth. In particular, knowledge about best practices recommended on the basis of scientific evidence and by the WHO and Brazil’s Ministry of Health increased significantly, especially among pregnant women. The degree to which participants had a positive perception about, and preference for, normal vaginal birth also increased after experiencing the intervention. Furthermore, even under the assumption that visitors to the SoB intervention might represent a particular group of individuals who favor normal birth, the percentage of individuals with a positive opinion  of vaginal birth increased from 77.1% to 96.3% after the intervention.16 In Brazil in 2005, a law was passed guaranteeing every women’s right to have a companion of choice during all stages of labor in every public and private hospital or birth center without any additional costs to the patient17; nevertheless, this right is not guaranteed in all hospitals. In a national survey of women after childbirth, Diniz et al.16 found that 25% of women did not have a companion during their hospital stay, although only 6% reported that they did not want a companion.Knowledge about vaginal birth and the right to a companion during childbirth were the two indicators that changed the most among the general visitors. Studies have shown that a birth companion is the most valued right for women during childbirth.19 Studies also show that women in Brazil are not informed about best practices in childbirth during pregnancy.21 One study considers that women “accept” having a cesarean to avoid mistreatment and violent procedures during childbirth or obstetric violence.20 Domingues et al.21 reported that the most frequent reasons for avoiding a vaginal birth are fear of pain and mistreatment during childbirth and perceived inability to have a vaginal birth.Previous studies in Brazil have shown that fewer than 30% of women report a preference for delivery by cesarean at the beginning of pregnancy, but almost 90% of pregnancies result in cesarean even though only 10% have a medical indication.19 Although the SoB postpartum population had similar characteristics, it had a lower rate of cesarean delivery and a lower rate of premature birth as compared with the national rates of 55.5% and 11.5%, respectively. Prematurity is a major concern, because it is the primary cause of neonatal death and also an important determinant of quality of life.22 Best practices are being implemented in public hospitals in Brazil, but there are challenges to change the private system to prevent unnecessary cesarean and iatrogenic prematurity.The rate of cesarean delivery is extremely high in Brazil, particularly in private hospitals (84.0%) and among high-income and highly educated women.23 and 68 204 followers on Facebook, 4505 on Instagram, and 2900 on a YouTube channel.24Educational interventions are useful both for improving knowledge about childbirth best practices and for empowering women to make informed decisions. The SoB proved to be an effective initiative that contributed to improved knowledge about childbirth and was associated with use of evidenced-based practices and women’s right to a respectful birth. It has also promoted social mobilization through a social network with a websiteIt is an inclusive, sensitive, and artistic intervention to engage society and disseminate accurate information to the population. Beyond the general public, it has specifically reached families with pregnant women, as well as adolescents, students and teachers of the public educational system, and health professionals at the primary healthcare and maternity level. These target populations are strategic to help change culture toward valuing normal birth as a tool to promote health and improve maternal and children indicators in Brazil. The main limitation of the study is that the visitors might not represent the general population. Neverthless, the study results showed a considerable change in knowledge, perception, and preferences of the visitors toward normal birth.The SoB intervention contributed positively to improvement in knowledge about best practices in childbirth. It also influenced changes in feelings about and perceptions of normal birth. Scale-up of this initiative should be explored to support changes in culture toward valuing normal birth, and thereby promote maternal and child health in Brazil and decrease unnecessary cesarean procedures and premature birth.


Preterm birth is defined as the birth of a baby before 37 completed weeks of gestation. Worldwide, prematurity is the second foremost cause of death in children under the age of 5 years. Preterm birth also gives rise to short and long term complications. Therefore, the primary aim of this study was to identify the factors associated with preterm birth in Wachemo University Nigist Eleni Mohammed Memorial referral hospital, Hadiya Zone, Southern Ethiopia.p < 0.05.An institution-based unmatched case-control study was conducted from July 01, 2018 to June 30, 2019 among mothers who gave birth in Wachemo University Nigest Eleni Mohammed Memorial referral hospital. A retrospective one-year data was retrieved from medical records of mothers with their index neonates. Simple random sampling technique was employed to recruit study participants. SPSS version 20 software was used for data entry and computing statistical analysis. Both bivariable and multivariable logistic regression analyses were used to determine the association of each independent variable with the dependent variable. Odds ratio with their 95% confidence intervals was computed to identify the presence and strength of association, and statistical significance was affirmed if The current study evaluated 213 medical records of mothers with index neonates (71 cases and 142 controls). Urban residency , antenatal care follow up , premature rupture of membranes , pregnancy induced hypertension  and multiple pregnancies  were the factors associated with preterm birth. More than one-third (36.6%) preterm neonates died in the present study.The present study found that urban residency, antenatal care follow up, premature rupture of membranes, pregnancy induced hypertension and multiple pregnancies were factors associated with preterm birth. The mortality among preterm neonates is high. Enhancing antenatal care follow up and early detection and treatment of disorders among pregnant women during antenatal care and undertaking every effort to improve outcomes of preterm birth and reduce neonatal mortality associated with prematurity is decisive.The online version contains supplementary material available at 10.1186/s12884-020-03503-9. The World Health Organization (WHO) defines premature baby as “babies born alive before 37 weeks of pregnancy are completed.” Each year, a projected 15 million babies are born preterm and this figure is increasing , 3.In 2014, 10.6% (9.0–12.0) was the estimated worldwide preterm birth rate, making a projected 14.84 million premature babies alive (12.65 million–16.73 million). Of these, 12 million (8.1%) preterm births took place in Asia and sub-Saharan Africa. In the sub-Saharan Africa the estimated preterm birth rate was 12.0 making the proportion of preterm birth 28.2% .Mothers who had antenatal care follow up had 92% reduced odds of developing preterm birth than those mothers’ who had no antenatal care follow up .Mothers who had premature rupture of membranes had odds 3.78 times higher to experience preterm birth than those who had no premature rupture of membranes .Mothers who had pregnancy induced hypertension had odds 3.77 times higher to experience preterm birth than those who had no premature rupture of membranes .Mothers who had multiple pregnancies had odds 5.53 times higher to develop preterm birth than their counterpart .The presented study was aimed to assess factors associated with preterm birth to confront neonatal morbidity and mortality related with prematurity. After controlling for confounders, urban residency, ANC follow up, premature rupture of membranes, pregnancy induced hypertension and multiple pregnancy were factors significantly associated with preterm birth.This study found that mothers who resided in urban areas had 52% reduced odds of developing preterm birth than those mothers’ resided in rural areas. This might be due to the fact that women living in urban areas have better access to the health care than in rural area which can play an important part in the prevention of preterm delivery.Besides, women living in rural areas are more likely to be exposed to hard labour and this increases the risk of preterm delivery particularly to women coupled with other risk factors for preterm delivery. Illiteracy which is more in rural area as opposed to urban area is also an important risk factor for preterm delivery. This finding is supported by other studies , 12.The present study also revealed that mothers who had antenatal care follow up had 92% reduced odds of developing preterm birth than those mothers’ who had no antenatal care follow up. This might be due to the fact that having antenatal care enhance health promotion, detect and prevent complications related with preterm delivery at earliest point. This finding is in line with studies done in central zone of Tigray , DebretaAccording to the present study, mothers who had premature rupture of membranes had odds 3.78 times higher to experience preterm birth than their counterpart. This might be due to the fact that prolonged premature rupture of membranes will favor microorganisms to ascend to the uterus causing intrauterine infection.The microorganism will break down the fetal membranes and also produce phospholipase which leads to formation of prostaglandin and endotoxin, substances that stimulate uterine contractions and causing preterm labour. This finding is similar with studies done in Kenya , NigeriaThe current study also verified that mothers who had pregnancy induced hypertension had odds 3.77 times higher to experience preterm birth than those who did not have pregnancy induced hypertension. This might be due to the fact that uteroplacental ischemia in the setting of pregnancy induced hypertension results in adverse pregnancy outcomes including preterm delivery and others. Besides, pregnancy induced hypertension is a frequent reason for terminating pregnancy at early gestation which results in preterm delivery. This finding is in line with studies carried out in Debretabour , Jimma , Kenya , NigeriaThe other factor associated with preterm birth is multiple pregnancies. Mothers who had multiple pregnancies had odds 5.53 times higher to develop preterm birth than their counterpart. This is due to the fact that multiple pregnancies cause distention of the myometrium leading to uterine contractions and cervical dilation.Moreover, other obstetric complications like preeclampsia and polyhydramnios concomitantly occur with multiple pregnancies resulting in spontaneous or iatrogenic preterm birth. This finding is consistent with other studies carried out in Tanzania , Kenya , CentralPreterm babies are predisposed to serious illness or death during the neonatal period. Deprived of appropriate treatment, those who survive are at increased risk of lifelong disability and poor quality of life. Complications arising from preterm birth are the main cause of neonatal mortality and the second prominent cause of deaths among children under the age of 5 years .According to the present study, 36.6% % of preterm neonates have died. The possible causes of death were a respiratory failure, apnea of prematurity, necrotizing enterocolitis and perinatal asphyxia. This finding is in line with study done in India in which perinatal mortality was 42.4% and respiratory distress, birth asphyxia and septicemia were common causes of death .The finding of the present study is also consistent with study conducted in Jimma University specialized hospital in which prenatal asphyxia, sepsis, jaundice, low gestational age, respiratory distress syndrome and initial temperature were factors associated with premature infant death .Limitations of the present study include; lack of information on body mass index, antenatal cortical steroids, monthly income and educational status due to retrieving data from secondary source. Larger sample have not been included in the present study due to lack of digitalization in handling of medical records of mothers in the study area  and therefore to include larger sample, bigger funds and longer periods are needed. Consequently, smaller sample included in this study have resulted in low and/or absence of some of the chronic medical conditions.The present study found that urban residency, ANC follow up, premature rupture of membranes, pregnancy induced hypertension and multiple pregnancies were factors associated with preterm birth. The mortality among preterm neonates is high. The possible causes of death were respiratory failure, apnea of prematurity, necrotizing enterocolitis and perinatal asphyxia.Enhancing ANC follow up and early detection and treatment of disorders among pregnant women during antenatal care is vital as this will reduce the occurrence of preterm birth. Every effort should be made to improve outcomes of preterm birth and reduce neonatal mortality associated with prematurity. Moreover, qualitative studies should be conducted to explore more factors causing preterm delivery and neonatal mortality associated with it.Additional file 1. Checklist used to assess determinants of preterm birth.


Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a biochemical marker significant for early prediction of acute kidney injury in adults. However, it has not been examined sufficiently among the infant population, particularly newborns in terms of reference values. The aim of our study was to determine the concentration of uNGAL in healthy term newborns and to determine if there was a difference in uNGAL concentration according to gender, postnatal age and birth weight.Our study involved 81 healthy term newborns birth . Urine NGAL was measured using chemiluminescent microparticle immunoassay (CMIA) within 72 hours after birth, on Architect plus ci8200 analyser . Data were analysed using Statistica software.st day, 28.9 ng/mL (16.5-64.2 ng/mL) 2nd day and 23.9 ng/mL (20.2-46.6) 3rd day, P = 0.863. Regarding birth weight for newborns < 3500 g, median concentration was 25.0 ng/mL (16.5-45.4 ng/mL) and for weight ≥ 3500 g 30.6 ng/mL (16.5-64.2 ng/mL), P = 0.455.The median concentration of uNGAL in the whole study group of healthy term newborns was 27.1 ng/mL (16.5-56.0 ng/mL) ; newborn boys, 27.9 ng/mL (16.5-61.0 ng/mL), P = 0.941). Median uNGAL concentration according to postnatal age expressed in days was 28.2 ng/mL (11.7-57.2 ng/mL) 1There were no significant difference in uNGAL concentration in relation to gender, postnatal age and birth weight. Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, LCN2, siderocalin, 24p3, is a 25 kDa molecular weight protein. It belongs to the lipocalin superfamily, which consists of proteins that transport small hydrophobic molecules such as lipids, steroid hormones and retinoids -12. TherThe present study was prospective and included 81 healthy newborn  born at University Hospital Mostar, Bosnia and Herzegovina, from April to October 2019. The study was approved by the Ethics Committee of the University Clinical Hospital Mostar  in adherence to the Declaration of Helsinki. Written informed consent was obtained from all parents after explaining the purpose of the study. The newborns included in the study were delivered from full-term pregnancies and inclusion criteria after clinical examination were as follows: gestational age at birth ≥ 37 weeks, Apgar score ≥ 8 in the first minute after birth, C-reactive protein (CRP) < 5 mg/L, normal physical and ultrasound examination  required by a neonatologist after the post-delivery examination. The leftover serum was used to determine CRP concentration, which was the including criteria for the study. Venous blood samples were collected in Micro sample tubes with gel  with Micro needles 23 G . CRP concentration was determined using a CRP Latex reagent kit  on Beckman Coulter Chemistry Analyser AU680 , controlled two times a day . Urine samples (3 – 5 mL) were obtained within 72 hours after birth in paediatric urine sterile collector for newborns with a birth weight over 2000 g  and centrifuged at 400 RCF over five minutes and stored at - 80 °C until analysis. Urine NGAL concentration was quantitatively determined using original manufacturer Architect Urine NGAL reagent kit . Non-parametric tests were used because the obtained data were not normally distributed (Shapiro Wilk test). Measurement data were indicated as median and interquartile range (from first (Q1) to the third quartile (Q3)), except for gestation age that is presented as median and minimum – maximum. To compare two groups, Mann-Whitney The study comprised 81 healthy term neonates, newborn girls (subgroup F) and newborn boys (subgroup M). The respective median gestational ages were 39 (37-41) weeks in females, and 40 (37-41) weeks in males. Median values with an interquartile range along with general characteristics of healthy newborns  differentiated by gender are shown in et al., included measurement of uNGAL in 38 term newborns when they were three days old. The median concentration of uNGAL was 88.1 ng/mL  method was significantly higher than ELISA (R&D Systems) . Also in their study, there wasn´t a significant difference regarding uNGAL value associated with gender (et al. and Lavery et al., showed a negative correlation between uNGAL and birth weight (et al. that showed no differences in uNGAL concentrations in regard to birth weight (et al. showed that postnatal age is associated with uNGAL concentration (et al. study that showed no differences in uNGAL concentration regarding postnatal age (The study demonstrated that there was no significant difference in uNGAL concentration in relation to gender, postnatal age and birth weight, which supports the hypothesis mentioned beforehand. There have been several studies that included uNGAL concentration measurement in a healthy newborn population. One of these studies, done by Chen


Elective repair epigastric hernia is a frequent minor surgical procedure. In most cases the hernial content is pre-peritoneal fat.We report the case of a patient with epigastric hernia containing part of a bile duct cyst.Bile duct cysts are often asymptomatic, but when symptoms are present they may include intermittent, recurrent epigastric or right hypochondrial pain; abdominal tenderness; fever and mild jaundice.The presence of a bile duct cyst within a hernia is a very rare finding, especially making the diagnosis through an epigastric hernia. This case report is the first of a bile duct cyst within an epigastric hernia. When symptoms are present, the most common are intermittent recurrent epigastric or right hypochondrial pain, abdominal tenderness, fever and mild jaundice . Nausea,Epigastric hernia is usually asymptomatic too, with localized pain being the main symptom when present. In obese patients the diagnosis can be difficult, but in thin patients a bulge may be seen or palpated . This is23 (12 liters) and confirmed that the epigastric hernia content contained part of the cyst  showed a cyst of 33 × 23 × 30 cm with content estimated at 12,000 cmthe cyst A, B.Fig.The patient was subjected to resection of the cyst, cholecystectomy and Mayo repair of the epigastric hernia . A supra3There is still controversy as to how exactly epigastric hernia occurs. Both the vascular lacunae hypothesis and the forceful contraction hypothesis are accepted as possible explanations for the etiology . Most ofThe most common symptoms of bile duct cysts are abdominal pain, fever and jaundice, but their diagnosis is often is an incidental finding. The incidental finding of an early stage gallbladder neoplasm allows, in most cases, a better prognosis . A suturIn a review of the literature, we searched the PubMed database for articles published up to July 2018 using the terms “hernia AND bile duct cyst”, “hernia AND gallbladder cancer” and “epigastric hernia AND cancer” and identified 161 articles. The titles and the abstracts of the articles were evaluated, but none of them reported something similar to our case.The presence of a bile duct cyst within a hernia is a very rare finding, especially making the diagnosis through an epigastric hernia. This case report is the first of a bile duct cyst within an epigastric hernia.There was no source of funding for this research. Any costs were covered by the authors.The Institutional Ethics Committee approval number is 2.819.549. Ethics committee approved this study with waiver of the signed consent term, since patient having her case reported lost follow-up after a few years, and it is no longer possible to contact her by phone. In addition, given the nature of the study, we will use only the information provided in the patient's medical record, the data will be analyzed in a way that will not make it possible for her to be identified, and there will be no discrimination team that could compromise his or her privacy or integrity.Written informed consent was not obtained from the patient. The head of our medical team has taken responsibility that exhaustive attempts have been made to contact the family and that the paper has been sufficiently anonymised not to cause harm to the patient or their family. A copy of a signed document stating this is availble for review by the Editor-in-Chief of this journal on request.Mauricio Alves Ribeiro: conception and design, acquisition of data. Literature research development of data set and write manuscript.Gabriel Lorente Mitsumoto: acquisition of data. Literature research development of data set and write manuscript.André Soares Gallo: acquisition of data.Luiz Arnaldo Szutan: conception and design. Final approval of the version to be published.Our manuscript is a case report not a research.Luiz Arnaldo Szutan, MD, PhD. Associate professor in the Surgery Department, at Santa Casa de Sao Paulo School of Medical Sciences, School of Medicine, São Paulo, Brazil. Head of the Liver and Portal Hypertension Group of Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo Brazil.Not commissioned, externally peer-reviewed.The authors declare that there are no conflicts of interest.