We found a statistically significant higher rate of abnormal neurodevelopment outcomes in non-Jews compared to Jews . Conclusions: We found a relatively high overall rate of CP in our local population and a significant difference in neurodevelopmental outcomes between Jews and non-Jews. This study emphasizes the need for an expanded and detailed national database collecting post-discharge outcomes, as well as an assessment of national healthcare resource allocation and inequalities in preterm infants’ post-discharge care.Background: Currently, no local database in Israel collects neurodevelopmental outcomes of very low birth weight (VLBW) preterm infants. We investigated neurodevelopmental outcomes in one district of the largest healthcare organization in Israel. Methods: A cross-sectional study including all VLBW (<1500 g) preterm infants born between 1 January 2006 and 31 December 2016 who were followed in any of seven child development centers in Israel’s Northern District. Data were retrospectively collected from the computerized medical record database. Results: Out of 436 participants, 55.1% had normal developmental outcomes. A total of 8.9% had cerebral palsy (CP), 12.2% had a global developmental delay (GDD), and 33.4% had a language delay. Out of the extremely preterm infants ( Preterm infants are at high risk for short and long-term neurodevelopmental impairment in the neuro-motor, cognitive, language, and behavioral domains . The estOver the past decades, rates of survival of extremely preterm infants have increased with no consistent improvement in neurodevelopmental outcomes. The greatest increase in survival rates occurred in extreme preterm infants born before 25–26 weeks of gestation [While in some countries, rates of CP are decreasing , in otheThe Israeli national database collecting data for very low birth weight (VLBW) preterm infants currently does not include post-discharge neurodevelopmental outcome data, and, to our knowledge, no local study exploring outcomes has been performed as yet. In this cross-sectional study, we investigated the neurodevelopmental outcome of children aged 3–13 years who were born preterm with VLBW (<1500 g) and were followed in one district of the largest healthcare organization in Israel, and examined the differences in outcomes between gestational age, weight, and ethnicity groups. Participants: “Clalit” Health Services (CHS) is the largest of four integrated healthcare organizations in Israel. The study population included all VLBW (<1500 g) preterm infants born between 1 January 2006 and 31 December 2016 who were followed in any of the 7 CHS child development centers in Israel’s Northern District—Haifa and Western Galilee county. Haifa is the 3rd largest city in Israel and has a large metropolitan area. In Western Galilee, most of the population lives in small villages, but there are a few large cities. Most of the population in Haifa is Jewish, and around 20% are Arab, both Christian and Muslim, as well as Druze . In WestAt the time of data collection, participants were between 3 and 13 years of age. Infants who were lost to follow-up and infants with major congenital abnormalities  or chromosomal anomalies were excluded. The study was approved by CHS’s Ethical Board.Data collection: Data were retrospectively collected from the computerized medical record database of CHS child development centers in Haifa and Western Galilee County. Demographic and perinatal data were extracted, including GA at birth, place of birth, mode of delivery, birth weight, ethnicity, etc., as well as complications of prematurity, including necrotizing enterocolitis (NEC), late-onset sepsis (LOS) patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), white matter injury (WMI), posthemorrhagic hydrocephalous (PHH), and retinopathy of prematurity (ROP), defined by commonly used published criteria ,15,16,17p < 0.05 was considered statistically significant. All analyses were performed using IBM Statistics version 24 (SPSS). Data analysis: Continuous variables are presented as means and standard deviations or as medians and ranges. Categorical variables are presented as percentages. The association between developmental outcomes and demographic and clinical characteristics was analyzed using the chi-square test for the categorical variables and the independent t-test or Mann–Whitney, as appropriate, for the continuous variables. Multivariable logistic regression was used to identify the factors associated with complications of prematurity. Odds ratios with 95%CI are presented. There were 469 VLBW preterm infants registered to any of the seven child development centers of the county. Twenty-eight were lost to follow-up, and four had major congenital abnormalities; one was due to congenital CMV infection, one had VACTERL association, one had polymicrogyria, and one had high suspicion of an undiagnosed congenital syndrome. Another child died after 2 years of follow-up (unknown etiology). A total of 436 infants comprised the final study cohort. In four infants, there were some incomplete data on the presence or absence of complications of prematurity. Demographic characteristics are presented in Out of all 436 patients, 55.1% had normal developmental outcomes. A third of the children had a language delay, 12.2% had a global developmental delay, 8.9% were diagnosed with CP, 7.8% had ADHD, and 1.6% were diagnosed with ASD .There was no association between neurodevelopmental outcomes and the center of birth or mode of delivery. There were three large birth centers with over 4000 annual deliveries and five small/medium centers with less than 4000 annual births. No significant differences were found in neurodevelopmental outcomes between infants born at large birth centers versus infants born at small/medium birth centers. There was considerable year-to-year variation in rates of all neurodevelopmental outcomes over the studied 10-year period with no consistent trend of rise or decline in any of the outcomes .p = 0.0001 for both). Only 40.3% of the preterm infants born between 23 and 27 + 6 weeks of gestation had normal development, compared to 57.7–59.1% of normal development in the other GA groups. Rates of neurodevelopmental impairments are presented by gestational age categories   .p < 0.0001) as well as with lower birth weight (p = 0.018). Out of all children with CP (N = 39), 56.4% were born at 23–27 + 6 weeks of gestation, 33.3% were born at 28–31 + 6 weeks, and 10.2% were born after 32 weeks. The rate of CP was 20.2% at 23–27 + 6 weeks of gestation (27.4% in infants < 26 weeks), 5.7% at 28–31 + 6 weeks, and 4.1% after 32 weeks of gestation. There were no cases of CP after 34 weeks. CP was associated with NEC and BPD  after controlling for birth weight and gestational age, as well as with IVH, WMI, and PHH . CP was significantly associated with younger GA ; however, autism spectrum disorder and hearing impairment or deafness were not. Language delay was also associated with BPD (p = 0.003), but this effect was lost after controlling for birth weight. Language delay and GDD were significantly associated with younger GA ; however, when adjusting for GA, this effect was lost. Language delay occurred at a higher rate in LGA versus SGA and AGA infants , but this finding did not remain significant after adjusting for GA as well. The rates of DCD, GDD, ADHD, and autism were not related to the weight percentile group.Considering the weight percentile for gestational age, the rate of CP was lower in SGA infants  compared to AGA  and LGA , and this was statistically significant , as well as ADHD , p = 0.005), and language delay , p = 0.001). There were no sex differences in rates of GDD, DCD, and autism.Sex differences were found in some of the neurodevelopmental outcomes. Males were more likely to be diagnosed with CP than females , p < 0.0001), as well as in the rates of CP , p = 0.022,), GDD , p = 0.002), and language delay , p = 0.001). Only DCD was less likely to be diagnosed in non-Jews than in Jews  p = 0.012). The mean number of visits to the child developmental center was slightly lower in non-Jews compared to Jews; however, this was not statistically significant .Comparing outcomes between Jews and non-Jews (mostly of Arab or Druze descent), we found strong evidence to suggest differences in abnormal neurodevelopmental outcomes, with non-Jews more likely to be abnormal compared to Jews , p < 0.1 in the univariate analyses , there was a significant association between any abnormal neurodevelopmental outcome and male sex ), non-Jewish ethnicity ), cystic WMI ), and high-grade IVH ), but not with other complications of prematurity. The same model found an association between GDD and cystic WMI ), high-grade IVH (p < 0.001 OR 9.7 (95%CI 2.8–33.1)), large for gestational age ), and NEC ). In a multiple logistic regression model adjusted for all variables with Preterm infants are a vulnerable population at high risk for mortality, morbidity, and neurodevelopmental impairments that carry lifelong consequences. In this study, we present the local rates of neurodevelopmental impairments in a large district in Israel. We found a relatively high rate of CP in our preterm population, even when considering the variations in the prevalence of CP across studies. Our overall local rate of 8.9% is higher than reported by other studies utilizing global data. Oskoui et al. found a prevalence of 6% in infants born less than 1500 g in their meta-analysis . In the The reason for our higher rate of CP is unclear. While CP in preterm infants is multifactorial, associations with chorioamnionitis, birth asphyxia, BPD, PDA, and severe brain lesions have been previously described ,27,28,29Language delay is common in preterm infants. Unlike the rate of 5–12% in children aged 2–5 years in the general population , StipdonUnlike some previous studies suggesting a negative impact of SGA on neurodevelopment ,34,35, tSevere brain lesions were in correlation with CP, GDD, and language delay, consistent with previous reports ,43. In on = 7). We found sex differences in the rate of CP, ADHD, and language delay, with boys affected more than girls. These findings are in agreement with previously published studies ,47,48 anWhen comparing the outcome of Jews versus non-Jews, we found that most neurodevelopmental outcomes were poorer in non-Jews, despite a similar rate of follow-up visits in child development centers. In Israel, around 78% of the population are Jews, while Arabs comprise the largest minority group, around 21%, and Druze constitute a much smaller minority group, around 1.6% of the general population . In geneThis study has collected data from patients born over a relatively long period of 10 years. Several changes in practice occurred over this time period, such as the growing use of non-invasive ventilation and minimally invasive surfactant administration worldwide, as well as the implementation of a national initiative for quality improvement that began in 2014 to reduce central line-associated bloodstream infection . This inOur study has several limitations. First, due to its retrospective nature, we could not account for many confounding variables such as maternal conditions, perinatal course, and postnatal exposures. We did not have available data on the family’s socioeconomic and parental education status. In addition, we were only able to collect data from the children who were followed in our child development centers, which introduces selection bias as VLBW preterm infants who were not CHS members could not have been evaluated in CHS’s child development centers. Furthermore, infants were referred to neurodevelopmental assessment at the discretion of the pediatrician so that subtle impairments may have been missed. Due to the retrospective cross-sectional nature of the study, we could only use the most recent available neurodevelopmental diagnosis and could not determine the average age at diagnosis. Due to the lack of current guidelines for developmental assessment, the children’s age at follow-up visits was not uniform. The strengths of this study lie in utilizing the large and reliable database of “Clalit” Health Services, which is the largest health service organization in Israel and one of the largest in the world, ensuring over 4.6 million people, and is by far the predominant health service organization in the Northern District of Israel. This allowed us to use a relatively large sample of patients who may likely be a representative sample reflecting the area’s population. Furthermore, all patients were at least 3 years old at the time of data collection, and 41% were over 6 years of age, thus increasing diagnostic accuracy compared to earlier evaluations. The importance of this study is the collection of our local neurodevelopmental outcomes for the first time on this scale.In Israel, perinatal and postnatal information on preterm infants born <1500 g is collected in the national VLBW infant database, which is part of a collaboration of international neonatal networks, the iNEO . The database includes maternal and neonatal information to discharge, but no data after discharge are currently collected ,56. IsraOur results should be interpreted within the framework of this study’s limitations. We have shown relatively high rates of CP and some group differences in neurodevelopmental outcomes in our population; however, causality cannot be detected in this cross-sectional retrospective design, and there was a lack of data on many confounding factors. Future well-designed prospective longitudinal studies should be performed to provide a more accurate picture of our local neurodevelopmental outcomes.In light of our results, the authors feel it would be prudent to expand national data collection and post-discharge guidelines and to further assess the national healthcare resource allocation in Israel and the provision of post-discharge care to preterm infants.Our study describes, for the first time, local neurodevelopmental outcomes of VLBW preterm infants after 3 years of age. We found a relatively high overall rate of CP and a significant difference in outcomes between Jews and non-Jews. This study emphasizes the need for an expanded and detailed local database of post-discharge outcomes and for assessment of national healthcare resource allocation and inequalities in the provision of care to preterm infants after discharge.


Brain glymphatic dysfunction is involved in the pathologic process of acute ischemic stroke (IS). The relationship between brain glymphatic activity and dysfunction in subacute IS has not been fully elucidated. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was used in this study to explore whether glymphatic activity was related to motor dysfunction in subacute IS patients.Twenty-six subacute IS patients with a single lesion in the left subcortical region and 32 healthy controls (HCs) were recruited in this study. The DTI-ALPS index and DTI metrics  were compared within and between groups. Spearman's and Pearson's partial correlation analyses were performed to analyze the relationships of the DTI-ALPS index with Fugl-Meyer assessment (FMA) scores and with corticospinal tract (CST) integrity in the IS group, respectively.t = −3.02, p = 0.004). In the IS group, a positive correlation between the left DTI-ALPS index and the simple Fugl-Meyer motor function score  and a significant negative correlation between the left DTI-ALPS index and the FA  and MD  values of the right CST were found.Six IS patients and two HCs were excluded. The left DTI-ALPS index of the IS group was significantly lower than that of the HC group  biomarker of motor dysfunction in subacute IS patients. These findings contribute to a better understanding of the pathophysiological mechanisms of IS and provide a new target for alternative treatments for IS. Ischemic stroke (IS) remains one of the leading causes of disability and death worldwide  and interstitial fluid (ISF) in the brain  is the primary descending motor pathway carrying movement-related information and has been widely studied after stroke  is a non-invasive method for evaluating glymphatic system function in individual subjects based on diffusion tension imaging  were recruited for this cross-sectional study. The inclusion criteria for patients with IS were as follows: (1) age being 18 years or older; (2) a single lesion in the left subcortical regions; (3) magnetic resonance (MR) images collected 7–40 days after stroke onset  were performed. Using a multiband sequence , a total of 129 DWI volumes were acquired, with 18 different b-values ranging from b = 0 to b = 3,000 s/mm2 and 128 different diffusion encoding orientations  with a 64-channel head/neck coil. Participants were placed in a supine position, and the coil was filled with a sponge pad to keep the head stationary during the examination. Conventional MR images (including T2-FLAIR images) were acquired to identify stroke lesions and other brain abnormalities. Diffusion spectrum imaging (DSI) scans were obtained with an echo planar imaging (EPI) sequence, and multiple ” build 13 January 2022, http://dsi-studio.labsolver.org). The FSL's   Smith,  eddy was) Smith,  with a dBased on measurement satisfaction, ROIs (volume size = 12 mm × 4 mm × 2 mm) were placed in the projection and association fiber regions of the bilateral hemisphere on the color-coded FA map in the horizontal plane of the lateral ventricle body  and association fibers (Dxx − assoc) on the x-axis and that of the projection fibers (Dyy − proj) on the y-axis and the association fibers (Dzz − assoc) on the z-axis as follows:The DTI-ALPS index was proposed by Taoka et al. , which wThe DTI-ALPS index was calculated for each subject to assess the activity of the glymphatic system in the native space.https://cran.r-project.org/, version 4.0) was used to perform demographic data analysis, intergroup comparison, and correlation analysis. All continuous data were reported as mean ± SD.R statistics software  in the IS group. Controlling for age and time since stroke onset, the correlation of the DTI-ALPS index with CST metrics was assessed using Pearson's partial correlation analysis.The relationship between the left ALPS and the left FA of CC and the right ALPS and the right FA of CC in the two groups was analyzed using Pearson's partial correlation analysis. In addition, the relationship between bilateral ALPS and the mean FA of bilateral CC was also analyzed.p-value was < 0.05, the results were considered statistically significant after multiple comparison corrections.If a n = 5) or the modified Fazekas scale for white matter hyperintensities >2 (n = 1), and two HC participants were excluded due to poor image quality. Finally, 20 IS  and 30 HCs  were included. The two groups were matched in terms of age  and gender . The demographic and clinical characteristics of participants are summarized in Initially, 6 of the 26 subcortical IS patients were excluded due to ischemic lesions involving ROI regions  and 1.381 ± 0.172 (right side); in the HC group, the index was 1.565 ± 0.197 (left side) and 1.454 ± 0.107 (right side) refer to .t = −3.02, p = 0.004), but the right DTI-ALPS difference between the groups was not significant .The left DTI-ALPS index in the IS group was significantly lower than the same side in the HC group . However, this effect was not observed in the IS group   .p = 0.019, p = 0.052) in the IS group. There was no significant association between the right DTI-ALPS index and simple Fugl-Meyer motor function score  and the Fugl-Meyer sensory score .We found that a higher left DTI-ALPS index was associated with a better simple Fugl-Meyer motor function score  and MD  on the left were reduced more than those on the right. There was no significant correlation between the bilateral CST metrics and simple Fugl-Meyer motor function score in patients with IS  and MD   and MD .After controlling for age and time since stroke onset, there were significant negative correlations between the left DTI-ALPS index and the white matter microstructure integrity indices of the right CST: FA (= 0.032) . There wR = 0.13, p = 0.57), the right DTI-ALPS index and FA of the right CC , the left DTI-ALPS index and the mean FA of the left CC , and the right DTI-ALPS index and the mean FA of the right CC . In addition, there was also no significant correlation between the DTI-ALPS index and FA of CC in the HC group . These findings suggest that ALPS can be an MR biomarker of motor dysfunction in patients with subacute stroke and shed light on possible medical interference for IS.Structural changes induced by strokes can significantly alter the characteristics of tissue water diffusion . We found that the integrity of CST on the affected side was impaired after stroke, which was consistent with a previous study (Peters et al., Diffusion tensor image metrics can be used as an imaging evaluation index for monitoring motor function impairment (Yang et al., In contrast to the result of a recent study (Zhang et al., To the best of our knowledge, this is the first study to investigate whether the ALPS index is affected by commissural fibers traveling in the left and right directions. There was no significant correlation between the FA values of the CC and the ALPS index in both the IS and HC groups. Based on the abovementioned preliminary results, we suggest that the ALPS index is an appropriate measurement in the present study and can reflect the state of the glymphatic system. Nevertheless, this preliminary conclusion needs to be further confirmed by more rigorous studies of large samples.b-value acquisitions, it may not be the optimal DTI-ALPS scanning protocol. According to a recent study (Taoka et al., This study has some limitations. First, the small sample size of this study requires prudence in interpreting the results. Second, although the onset time of IS was 7–40 days, most of them were concentrated within 20 days, and glymphatic function may change over time, which may have some impact on the findings (Toh and Siow, In conclusion, a decreased DTI-ALPS index indicates glymphatic system dysfunction in patients with subacute IS and may serve as an MR biomarker for motor dysfunction in these patients. These findings could help us understand the pathophysiological mechanisms of IS and develop alternative treatment options for post-IS glymphatic activity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Medical Research Ethics Committee of Xi'an Daxing Hospital. The patients/participants provided their written informed consent to participate in this study.YQ: conceptualization, investigation, and writing—review and editing. XinL: writing—original draft. YaQ: investigation and data curation. HZ: data curation. YiQ: software and visualization. XiaL, YZ, and WH: investigation. LW: conceptualization, methodology, software, and writing—review and editing. MZ: conceptualization, supervision, and writing—review and editing. All authors contributed to the article and approved the submitted version.


Maternal exposures to environmental hazards during pregnancy are key determinants of birth outcomes that affect health, cognitive and economic status later in life. In Ethiopia, various epidemiological evidences have suggested associations between environmental exposures such as household air pollution, cigarette smoking, and pesticide exposure and pregnancy outcomes such as low birth weight, preterm birth, and birth defects.This review aimed at generating summarized evidence on the association between maternal exposure to environmental factors  and pregnancy outcomes  in Ethiopia.A systematic literature search was performed using PubMed, Google Scholar, and the Cochrane Library databases. All observational study designs were eligible for inclusion in the review. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS) quality assessment tools adopted for case-control and cross-sectional studies. The random-effects model was applied in computing the pooled estimates and their corresponding 95% confidence interval (CI). Funnel and Doi plots were used for detecting the potential publication bias. All statistical analyses were performed using comprehensive meta-analysis (CMA 2.0) and MetaXL version 5.3 software.The pooled estimates revealed that prenatal biomass fuel use increased the risk of giving a low birth weight baby by twofold , and has no separate kitchen increases the risk of having low birth weight baby nearly by two and half times . Overall, using biomass fuel as the main energy source for cooking and /or having no separate kitchen from the main house is 2.37 times more likely to give low birth weight babies . Active cigarette smoker women were 4 times  more prone to have low birth weight babies than nonsmokers; and passive smoker women were 2.6 times  more risked to give low birth weight babies. It was also estimated that active cigarette smoker women were nearly 4 times  more likely to give preterm birth babies. Pesticide exposure during pregnancy also increases the risk of the birth defect 4 times  compared with non-exposed pregnant women.Household air pollution from biomass fuel use, active and passive cigarette smoking, and pesticide exposures are significantly associated environmental risk factors for low birth weight, preterm birth, and birth defects in Ethiopia. Therefore, Pregnant and lactating women should be aware of these environmental hazards during pregnancy. Promoting clean energy and improved and efficient stoves at the household level will help to reduce household air pollution-related adverse health effects.CRD42022337140.PROSPERO 2022:  The pregnancy period is a crucial determinant of an infant’s health and survival for years to come , 2 whichPrenatal exposure to various classes of chemicals, including household air pollution, cigarette smoking, and pesticide exposure evidenced to have an association with adverse pregnancy outcomes –9. StillThough maternal characteristics and obstetric practices play an important role in contributing to adverse birth outcomes, several environmental risk factors have been studied for possible roles in influencing pregnancies and resulting in adverse birth outcomes which have a significant impact on mortality, morbidity, and healthcare costs , 4, 14. In Ethiopia, the evidence on the association between environmental pollution and adverse pregnancy outcomes is particularly strong for low birth weight, preterm birth, and birth defects with exposure to household air pollution , 16, 17,It is also common to see Ethiopian women engaged in different agricultural, industrial, and other activities until their late pregnancy period which led to maternal exposure to chemicals in the workplace before and during pregnancy , 26. BecThough the body of scientific evidence links these environmental exposures with adverse pregnancy outcomes, the impacts have received less attention from clinicians compared with other maternal factors , 30. TheThis paper aims to synthesize and generate the current pooled evidence from available epidemiological studies on environmental exposures and adverse pregnancy outcomes to facilitate further utilization of the evidences in Ethiopia.This systematic review and meta-analysis was registered on PROSPERO with a protocol number CRD42022337140.Firsthand studies published in peer-reviewed journals were searched systematically using PubMed, Google Scholar, and the Cochrane Library databases. Repositories in Ethiopian universities were also visited for unpublished studies. Additional publications were identified based on references cited within the eligible studies. Internet (using the Google search engine) was also searched to maximize search efficiency. The above databases were searched following the new version of Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline for reporting protocol  and the Boolean operators like “AND”, and “OR” were used to maximize the sensitivity and specificity of our search strategy by bringing key concepts together to identify environmental exposures and pregnancy outcomes search in the PubMed database. The improvement of the search terms was made while doing a trial among randomly selected articles and looking for other relevant terms within each concept from retrieved papers. After some rounds of trial and refinement of the search term, we formulate the final search term for PubMed as follows; (Pregnant women) OR (gravida)) OR (delivering women)) AND (indoor air pollution)) OR (biomass fuel use)) OR (solid fuel use)) OR (kitchen smoke)) OR (wood burning)) OR (household air pollution)) AND (cigarette smoking)) OR (passive smoker)) OR (active smoker)) OR ) AND (pesticide exposure)) OR (herbicide use)) OR (use of insecticides)) OR ) AND (pregnancy outcomes)) OR (low birth weight)) OR (preterm birth)) OR (stillbirth)) OR ) OR (birth defect)) OR ) OR ) AND (Ethiopia).Since some databases do not support the use of Boolean or quotation, a standard search strategy is used only in PubMed, then later it is modified according to each specific database to get the best relevant results. Therefore, we modified the initial search terms for each database to get appreciated results. The detailed search strategy for each database is found in as The search was built based on the population, exposure, and outcome (PEO) research question formulation strategy. Articles published up to May 30, 2022, from the multiple database searches were collated and duplicates were removed. All articles resulting from the databases were imported into one endnote library and duplicates were removed.All observational studies  reported the association between environmental exposure  and adverse pregnancy outcomes  and conducted in Ethiopia were eligible for this systematic review and meta-analysis. Studies published Up to May 30, 2022, only in the English language were included mainly to avoid mistakes in the translation process. Other studies were excluded due to the following reasons: (a) articles that did not provide calculably or reported ORs and 95% CIs, (b) review studies, (c) none related to the above specified environmental exposures and pregnancy outcomes, and (d) animal or case studies.Three authors  independently assessed the risk of bias for each article using the Newcastle–Ottawa Scale (NOS) quality assessment tool  . This scAll the necessary data were extracted using a customized form based on the Cochrane Public Health Group data extraction form and cross-checked to avoid errors. The data extraction forms were designed to be tailored to the review questions. One author (HD) developed the first draft of the data extraction form to gather information on the items of interest. This was reviewed by ST and complemented and revised after discussion. Two authors (BG and AB) piloted the data extraction forms and extracted the information of interest from the included studies using the final version of the extraction form. One of the major modifications added after piloting the data extraction form was the formulation of the additional table  containiThe variables extracted were determined based on the review questions. Extracted data items were cross-checked between the reviewers, with any disagreement being resolved through consensus or via arbitration by a third reviewer if necessary (HD). The data extraction format was designed to include first author, publication year, study type, sample size, types of exposure, types of birth outcome (low birth weight and preterm birth), odds ratio with 95% CI and publication history . In addiThe outcome of this review is to determine the association between prenatal exposure to environmental risks  and adverse pregnancy outcomes  as these are the most reported variables. Household air pollution exposure was assessed qualitatively based on the types of fuel used in the households, the location of the kitchen from the main house, the presence of windows, cooking frequency, and time spent in the kitchen. The comparison was made between low-pollution fuels , and biogas) and high-pollution fuels . Whereas cigarette smoking and pesticide exposures were assessed based on the self-reported response of the respondents about their exposure statuses an active or passive smoker or nonsmoker and pesticide user or nonuser. The pooled odds ratio with its 95% CI was calculated based on outcomes from the primary studies. All exposure and outcomes ascertainment techniques for each study are reported in a separate table .2 statistics with its p-value. As heterogeneity between studies in design, geographic location, exposure to different biomass fuels, different outcome measurement methods, different confounding factors, and methodological differences are expected, a random-effects meta-analysis model was used to compute the pooled estimate. The standard errors of the studies were plotted to detect asymmetry in the distribution of studies.All relevant extracted data were analyzed using comprehensive meta-analysis (CMA 2.0) and MetaXL version 5.3 software. Heterogeneity among included studies was assessed using Cochran’s Q test and IIn addition, the Doi plot  with Luis Furuya-Kanamori (LFK) index was used to assess publication bias. Because the Doi plot is more visible than the funnel plot to observe the symmetricity of the two areas of the graph and the LFK index is more sensitive than Egger’s regression to detect publication bias. LFK index <1 indicates no asymmetry, between 1 and 2 suggests minor asymmetry, and index >2 suggests major asymmetry . Pooled Initially, we identified 820 studies in our search. But only 17  studies with 18,560 mother-infant pair participants were selected for data extraction as summarized in the PRISMA flowchart . Three sLow birth weight infants are defined as weighing less than 2,500 grams at birth . Birth wSensitivity analysis was performed step-by-step leave-one-out method to assess the impact of each primary study on the pooled OR and to detect the possible causes of heterogeneity between studies. After the exclusion of the highest OR 3.83, the pooled value reduced to 1.76 , and with the additional exclusion of the lowest OR study, 1.70 the pooled value became 3.19 . This indicates no significant outlier from the studies. In addition, Doi plots were used for detecting potential publication bias. The plot was asymmetrical with (LFK index = 5.07), suggesting major asymmetry. Accordingly, the results indicated the presence of potential publication bias .As cooking behavior is an important factor, it was considered in this review and the above studies were pooled to generate the association between cooking in a non-separated kitchen and low birth weight. The pooled odds ratio showed that infants from mothers who were cooking in the non-separated kitchen in the main house were nearly twice more likely to give birth with low birth weight babies than those who were cooking in separated kitchens from the main house . The overall odds of giving low birth weight babies among biomass fuel users and/or having no separate kitchen for cooking was estimated to be (OR = 2.37 (95% CI: 1.59–3.53) .It is also evidenced that infants born to active or passive cigarette smoker mothers weigh substantially less , 50 and The sensitivity of each study was checked to identify smaller or larger reported odds ratios that could affect the pooled estimate by varying instability. But, the sensitivity analysis of this review showed no study has significantly affected the pooled result ranging from  to . To detect the potential publication bias for this group of studies, the Funnel and Doi plots were used. As a result, the asymmetry funnel plot suggested publication bias exists among these included articles . This mePreterm birth is a live birth before 37 completed weeks of gestation . Three sSuggestions are also growing and revealing that exposure to pesticides during pregnancy increased the risk of certain types of birth defects , 27, 53.The Doi plot with (LFK = 1.07) demonstrates the presence of minor symmetry with apriori concern about negative publication bias (studies showing a negative effect of pesticides more likely to be published) . In contThis study was conducted to examine the association between environmental exposure during pregnancy and pregnancy outcomes in Ethiopia. Environmental exposures included in this review are biomass fuel use for cooking, heating, and lighting, active and passive cigarette smoking, and exposure to pesticides. The pooled odds ratio in this review indicated that prenatal exposure to air pollution from biomass fuel increases the risk of giving a low birth weight baby by twofold.The result is in agreement with a growing body of both epidemiological and toxicological research that links household air pollution from biomass fuel use with increased risks of low birth weight and preterm birth –58. The The possible plausible mechanism for the observed association can be explained in different ways hypothesized by different researchers , 64. OneCurrently, it seems to be evidenced that maternal exposure to cigarette smoke (both active and passive) during pregnancy contributes to adverse pregnancy outcomes including a decrease in birth weight , 66, 67.In this review, the pooled OR was computed from three studies , 36, 37 Though scientific evidence is surplus on the influence of multiple medical and socioeconomic statuses of pregnant women on birth defects, it is also suspected to be associated with exposure to pesticides. Wide-ranging research worldwide has identified potential associations between in-utero pesticide exposure and several adverse birth outcomes . This st2 test for heterogeneity should be interpreted very cautiously.Our effort to maximize the search efficiency during retrieving all available relevant literature could be mentioned as the main strength of this paper. But, the number of original studies conducted on environmental exposure and pregnancy outcomes is very limited in Ethiopia. This may potentially affect the magnitude of pooled estimated values. The way the selected studies measured the exposure status and outcome variables differed, which potentially has an impact on the summary results due to misclassifications. Some confounding factors, such as the type of cooking stoves, personal exposure, and the availability of windows or chimneys also remained uncontrolled in some studies. In addition, since this review is based on the available observational  studies, all the methodological and statistical limitations of the primary studies have an impact on the quality of this systematic review and meta-analysis work. Especially, recall and selection bias cannot be eliminated. Since the number of studies included in this systematic review and meta-analysis work is relatively small (< 20), the Chi-squared statistical test (Q test) and the IHousehold air pollution from biomass fuel use, active and passive cigarette smoking, and pesticide exposure is associated with environmental risk factors for low birth weight and birth defects in Ethiopia. Pregnant women living in households that utilize biomass fuel or are exposed to cigarette smoke were more at risk of giving low birthweight babies than mothers who live in households that utilizes clean energy sources or non-cigarette smokers. In this review. it is also evidenced that pesticide exposure has a positive association with birth defects including neuro tube defects. Therefore, Pregnant and lactating women should be aware of the risks of indoor air pollution, pesticide exposure, cigarette smoking, and another environmental risk factor during their pregnancy period. Promoting clean and effective solid fuels and improved and efficient stoves at the household level will help to reduce household air pollution-related adverse health effects, specifically low birth weight. Future studies should pay more attention to effective exposure measurement including personal and biomarker sampling for different environmental pollutants during the whole gestation period.Adverse pregnancy outcomes including low birthweight, preterm birth, neural tube defect, and congenital anomalies are significant public health problems in Ethiopia. Because of Exposure of women to various environmental chemicals  before and during pregnancy leads women to inhale them for hours which consequently leads to adverse pregnancy outcomes. Despite the progress made to reduce the burden of maternal and infant mortality and morbidity in the country, the magnitude of these adverse pregnancy outcomes is still one of the challenges that need to be addressed. Identifying the association between biomass fuel use, cigarette smoking, and pesticide use with pregnancy outcomes can help the efforts to revise, amend or implement treatment guidelines for the clinician and contribute valuable imputes for policy and decision-makers.S1 Checklist(DOCX)Click here for additional data file.S1 Data(XLS)Click here for additional data file.S2 Data(CSV)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


FFM (p < 0.001) and weight growth velocity (p = 0.022) were significantly lower in IUGR compared to AGA infants, but equal in SGA and AGA infants. FM was not significantly different between all groups. (4) The FFM Z-score was significantly lower in IUGR compared to AGA infants (p = 0.017). Being born constitutionally small compared to AGA had no impact on growth and body composition. These data showed that early aggressive nutritional management is essential in IUGR infants to avoid impaired growth and loss of FFM.(1) Intrauterine growth restriction (IUGR) is associated with multiple morbidities including growth restriction and impaired neurodevelopment. Small for gestational age (SGA) is defined as a birth weight <10th percentile, regardless of the etiology. The term is commonly used as a proxy for IUGR, but it may represent a healthy constitutionally small infant. Differentiating between IUGR and constitutionally small infants is essential for the nutritional management. (2) Infants born at <37 weeks of gestation between 2017 and 2022, who underwent body composition measurement  at term-equivalent age, were included in this study. Infants with IUGR and constitutionally small infants (SGA) were compared to infants appropriate for gestational age (AGA). (3) A total of 300 infants (AGA:  Intrauterine growth restriction (IUGR) is well known to be associated with increased neonatal morbidity and mortality ,2,3. A rIUGR is defined as a fetus that has failed to reach its growth potential, which can be due to several conditions, but is primarily caused by placental insufficiency and is characterized by impaired oxygen and nutritional supply ,18. The The difference between infants with IUGR and constitutionally small infants has not been considered in neonatal treatment concepts ,33. IUGRTo the best of our knowledge, there are no studies evaluating growth and body composition in preterm infants with IUGR in comparison to constitutionally small infants, which might have a relevant impact on future nutritional care and strategies of these infants. The aim of this study was to evaluate growth and body composition at term-equivalent age with a consideration of nutritional management in IUGR and constitutionally small infants compared to preterm infants appropriate for gestational age (AGA).This exploratory retrospective cohort study was performed at the Department of Pediatrics and Adolescent Medicine, Division for Neonatology, Intensive Care Medicine and Neuropediatrics at the Medical University of Vienna, Austria. The study was approved by the Ethics Committee of the Medical University of Vienna (Number: 1602/2019). The primary objective of this study was to evaluate growth parameters including weight, length, and head circumference at birth and at term-equivalent age as well as a body composition measurement (FFM and FM) at term-equivalent age in constitutionally small infants (SGA group) and preterm infants with IUGR (IUGR group) in comparison to a control group of preterm infants appropriate for gestational age (AGA group). The study was conducted at a level IV neonatal intensive care unit.®, Cosmed, Concord, CA, USA) to determine body composition (FFM and FM) at term-equivalent age, were enrolled in the study. Exclusion criteria were chromosomal abnormalities or genetic and metabolic disorders. In our hospital, body composition measurements are performed in all preterm infants at term-equivalent age as part of our standard clinical practice. Group assignment  was based on weight percentile and signs of placental insufficiency determined by prenatal ultrasound [Preterm infants born before 37 weeks of gestation between the years 2017 and 2022, who underwent air displacement plethysmography , body composition can be carried out in less than five minutes and without anesthesia [Air-displacement plethysmography (ADP) belongs to the two-compartment model of body composition that measures the density and volume of the subject and provides information about FFM and FM . Using testhesia . The advesthesia . Pretermesthesia . FFM andData on growth including weight, length, and head circumference were obtained retrospectively and analyzed from birth until term-equivalent age. Weight (g/kg/day), length (cm/kg/day), and head circumference (cm/kg/day) gain velocity were calculated from birth until term-equivalent age. Z-scores and percentiles for weight, length, and head circumference were calculated using Fenton growth charts  and WHO Body weight was measured daily with an electronic scale and when the infant reached 1000 g, body weight was measured every 48 h. In addition, supine length was measured using an infant length board, and head circumference was determined using a flexible cloth measuring tape.Intraventricular hemorrhage (IVH) was defined according to Papile et al.  and necrEnteral nutrition with mother’s milk or, if not available, pasteurized preterm single donor milk (holder pasteurization) or preterm formula (in infants >32 weeks of gestation) was started on the first day of life and increased by 20–30 mL/kg/day. Fortification of the enteral nutrition with bovine-based fortifiers  in infants >26 weeks of gestation or human milk-based fortifier  in infants <26 weeks of gestation occurred at an enteral intake of 100 mL/kg/day. Preterm infants also received parenteral nutrition starting on the first day of life. Carbohydrate, protein, and fat intake was administered according to the recommendations of ESPGHAN . Parentep-value of less than 0.05 was considered statistically significant.The demographic information and descriptive statistics were presented using the frequency distribution, median, and interquartile range (IQR). The weight, length, head circumference, FFM, and FM measurements were standardized into Z-scores using the LMS method, based on growth charts specific to sex and gestational age . A multin = 249, IUGR: n = 40, and SGA: n = 11). The body composition measurement was not performed in four infants due to following conditions: continuous oxygen requirement: n = 1, IUGR group; hemodynamic instability: n = 1, AGA group; and loss of follow up: n = 2, AGA group (p < 0.001), and not significantly different between SGA infants  and AGA infants , (p = 0.21). The anthropometric parameters  at birth were significantly lower in SGA compared to AGA infants  and significantly lower in IUGR compared to AGA infants , as expected  and SGA versus AGA (p = 0.09). At discharge, the median weight (p < 0.001) and length (p < 0.001) were significantly lower in infants in the IUGR group compared to the AGA group. The head circumference was not significantly different between the IUGR and AGA groups (p = 0.10). There were no significant differences in anthropometric parameters including weight, length, and head circumference at discharge between the SGA and AGA groups (p = 0.022). The weight growth velocity was not significantly different between the SGA and AGA groups (p = 0.74). There was no statistically significant difference in the median increase of length and head circumference from birth until discharge between the IUGR and AGA groups  and the SGA and AGA groups   .p = 0.68, and SGA versus AGA, p = 0.07). The enteral and parenteral nutritional supply  were not significantly different between the groups .The nutritional parameters are displayed in e groups . The ente groups . There wp = 0.38, and SGA versus AGA, p = 0.91.p = 0.017 and p < 0.001, respectively), while there were no significant differences in the FFM Z-Score and FFM gram between SGA and AGA infants   and weight at term-equivalent age and the study groups , while adjusting for the covariates such as sex, gestational age at birth, and age, weight, and length at measurement to adjust for body size. The FFM Z-score and FFM gram were significantly lower in infants with IUGR in comparison to AGA infants (ctively) . The FM ctively) . Sex didThis study evaluated growth and body composition at term-equivalent age in preterm infants with IUGR and constitutionally small infants in comparison to AGA infants. The FFM Z-Score and FFM gram were significantly lower in infants with IUGR in comparison to AGA infants, while there were no significant differences in FFM Z-Scores and FFM gram between SGA and AGA infants. The FM Z-Scores and FM gram were not significantly different in IUGR and SGA infants compared to AGA infants. The weight growth velocity from birth to discharge was significantly lower in the IUGR group than in the AGA group. There were no significant differences in growth velocity between the SGA and AGA groups.These data demonstrate that the weight growth and FFM were significantly lower in IUGR infants compared to AGA infants at term-equivalent age. Being constitutionally small compared to AGA had no significant impact on growth and body composition at term-equivalent age. The study underlines the importance of distinguishing between IUGR and infants being born constitutionally small. Moreover, these results are essential for the nutritional treatment concepts in constitutionally small infants, and aggressive nutritional management can be refrained from in these infants.The terms IUGR and SGA are often used synonymously in newborns, but the underlying pathomechanism and etiology of these patterns are related to different growth ,51. IUGROptimized nutritional management, quality of growth, and neurological outcomes are highly related to each other. Bruno et al.  showed tThe ESPGHAN recommends feeding enhanced nutrients up to the 52nd week of gestation in all infants below the 10th percentile at term-equivalent age, regardless of the pathology . HoweverIn our study, the weight at birth was significantly lower in SGA infants in comparison to AGA infants. Importantly, the weight growth velocity from birth until term-equivalent age and body composition, especially FFM, were significantly lower in IUGR compared to AGA infants. The median FFM Z-Score was −0.6 lower in the IUGR group in comparison to the AGA group at term-equivalent age. These data are consistent with the literature and underline that adequate nutrition is essential to avoid EUGR ,15. PoorOn the contrary, the growth velocity and body composition, especially FFM, are not significantly different between constitutionally small infants and AGA. Several studies explored the optimum nutritional management, especially protein intake, to avoid growth restriction ,10,11. Wn = 14) with that of AGA infants (n = 68). FFM was significantly lower in IUGR infants and these results are consistent with our study. These data emphasize that EUGR is still a significant challenge for neonatologists, and early aggressive adequate nutritional management is important to avoid long-term morbidities in these infants. However, the optimum nutritional management in IUGR infants is still unclear. Randomized controlled trials with nutritional interventions are needed to investigate adequate nutritional intake in these infants. However, two studies [n = 46) compared to AGA infants (n = 165). Notably, SGA was defined as birth weight below the 10th percentile, and no distinction between IUGR and constitutionally small infants at birth was performed. As already discussed in detail, the distinction between IUGR and constitutionally small infants is of major importance and should be diligently carried out. Therefore, a comparison between the meta-analysis and our study is not appropriate. In our study, a differentiation between IUGR infants and constitutionally small infants was well performed and further studies are necessary to evaluate the long-term effect on growth, body composition, and neurodevelopment. Interestingly, short-term outcomes including ROP, NEC, IVH, culture-proven sepsis, and BDP were not significantly different between the groups, especially not between IUGR and AGA infants. Previous studies showed that IUGR infants have a higher risk of neonatal morbidities [p < 0.001). We postulated that this observation might explain these results.A recent systematic review and meta-analysis evaluated growth and body composition in primarily term infants with IUGR and infants born SGA compared to AGA infants . Three s studies ,72 in thbidities . Howevern = 11) is relatively low and the comparison with the AGA group should be interpreted with caution. Further studies with a larger sample size and power calculation are necessary to draw final conclusions. However, this is the first study that distinguished between IUGR infants and constitutionally small infants, and evaluated the effect on growth and body composition. Furthermore, this study provides novel insights into growth and body composition in constitutionally small infants. Follow-up neurodevelopmental assessments using the Bayley Scales of Infants and Toddler Development at two and three years of age, as well as the Kaufman Assessment Battery of Children at five and a half years of age, will provide insight into growth and long-term neurodevelopment. A strength of our study is the use of body composition to accurately measure qualitative growth (FFM and FM) at term-equivalent age.One limitation of the study is the relatively small sample size and the retrospective nature of this study. We considered a matching process, but the sample size in this study is relatively small, because being constitutionally small is an exceedingly rare condition and gestational age at birth varied widely. Therefore, we incorporated gestational age at birth as a covariate in the multivariable regression analysis. However, designing and conducting a clinical trial with an adequate number of constitutionally small infants would be very challenging. Furthermore, these data are generated from an exploratory study and the analysis requires cautious interpretation. The sample size of infants in the SGA group (This study found that the weight growth velocity from birth to discharge was significantly lower in the IUGR group than in the AGA group. The FFM Z-Score and FFM gram were significantly lower in infants with IUGR in comparison to AGA infants, while there were no significant differences in FFM Z-Scores and FFM gram between SGA- and AGA infants. The weight growth velocity from birth until discharge was not significantly different between healthy constitutionally small infants and AGA infants. We confirm that growth velocity and FFM are suitable parameters on which to base the nutritional management of neonates. Our data show that the differentiation of IUGR and constitutionally small infants is important for nutritional management, especially for infants with IUGR. Early aggressive nutritional management is essential in IUGR infants to achieve optimum growth and development but might not be beneficial for constitutionally small infants.


Objective: To evaluate the prevalence of strabismus in premature children after the screening for retinopathy of prematurity (ROP) and to determine whether the level of prematurity (birth weight and gestation age) can be used as a predictor for both strabismus development and disease activity. Methods: This is a retrospective study, conducted in the Clinic for Eye Disease, section for Pediatric Ophthalmology of the Clinical Centre University of Sarajevo during the period from December 2013 until January 2017. 126 patients were involved. The inclusion criteria were gestational age ≤ 34 weeks, birthweight ≤ 2000 g and performed screening test for ROP. Patients were divided into three groups: patients without ROP, patients with spontaneous regression and patients with active ROP.Results: 52.4% patients were suffering from strabismus . All the patients with active ROP had esotropia (60.0%). The average birth weight and gestational age were lower in patients with strabismus (1371.3 ± 58.0 g and 29.7 ± 0.4 weeks respectively). Conclusion: Lower gestational age and birth weight of premature children showed the increased probability of strabismus development especially esotropia. Prematurity level was significantly lower in patients with active ROP compared to the rest of the patients.Abbreviations: ROP = Retinopathy of prematurity, ICROP = International Classification of Retinopathy of prematurity, BCVA = best corrected visual acuity  The development of Neonatal care units worldwide has increased a survival rate in prematurely born children. Premature birth leads to different systemic sequalae, including ophthalmological ones. The most important one is the retinopathy of prematurity (ROP), which can then increase the prevalence of other ophthalmological conditions, including refractive anomalies, strabismus, visual impairment, amblyopia, color vision impairment and visual field defects and nystagmus as the most frequent [2]. There are different risk factors for the development of ROP, among which gestation age, birth weight and oxygen therapy are the most important [3]. Other, less investigated, factors include anemia, apnea, mechanical ventilation, surfactant therapy, etc. [4].As the incidence of ROP has increased, it became one of the most investigated topics around the world [The aim of this research was to evaluate the prevalence of the active form of ROP and strabismus in prematurely born children. We also aimed to determine whether the level of prematurity (birth weight and gestation age) could be used as a predictor for both strabismus development and disease activity.5]. The guidelines of International classification of retinopathy of prematurity (ICROP) were used for the determination of the follow-up’s frequency [6].This is a clinical, descriptive, retrospective study, conducted in the Clinic for Eye Disease, section for Pediatric Ophthalmology of the Clinical Centre University of Sarajevo. The total number of patients was 126. All the patients were prematurely born and were screened for ROP during the period from December 2013 until January 2017. They also had regular follow-ups during the one-year period after screening. The screening was performed following German guidelines, starting 6 weeks after birth and by performing regular follow-ups until either full retinal vascularization or disease regression . The difference can be explained by the different inclusion and exclusion criteria, different time of follow-up, higher number of patients with an active form of the disease and different study designs. However, when compared to strabismus prevalence in full-term children (0.7-9.9%), all results from similar studies showed a significantly higher prevalence of strabismus in prematurely born children [9]. Strabismus diagnosis was determined during the period of follow-ups since it is sometimes hard to make a diagnosis in children younger than six weeks due to the decrease in coordination of the ocular movement. It is of utmost importance to recognize strabismus and to start the treatment in the early age with either conservative or surgical method to provide a proper visual development and prevent amblyopia. Our study also showed that the prevalence of strabismus was higher in children who were prematurely born. The study of Fieß et al. [7]. Their study also showed the correlation between strabismus and hyperopia, with esotropia being more related to it than exotropia. Many other studies also confirm our findings [10]. Even though the topic has not been fully investigated yet, some studies explain strabismus development in a connection to the presence of active ROP, increased incidence of refractive anomalies and neurological conditions, such as brain injuries, which are more frequent in premature children [11-13].Overall, esotropia was more frequent in our study compared to exotropia in these children, especially in the active form of retinopathy of prematurity, in which all patients developed esotropia. Fieß et al. have also reported esotropia as a more frequent type of strabismus [8].VanderVeen et al. reported that most children who were diagnosed with strabismus at the time of examination remained with this diagnosis, but some children managed to stabilize the alignment, even without the surgery [14] reported a higher prevalence in strabismus in patients with low gestational age, while Gulati et al. [15] reported the higher prevalence in patients with low birth weight and no association with gestation age. The average birth weight in our study was the highest in patients with orthophoria. The lowest was in exophoria, even though esophoria had the lowest minimum birth weight. The average gestation age showed the same trend as birth weight, but with a very small difference. Our results are consistent with other studies that indicate birth weight as a more significant predictive factor for strabismus . Fieß et al. reported a strong association with strabismus of both gestation age and birth weight [7]. This means that as the infant is born early and has a lower gestation age, there is a higher risk of developing one of the ocular complications, such as strabismus. There are several studies with the same objectives as in our study and some of them reported different results. Cotter et al. [The most significant results of this study were the impact of low gestation age and birth weight on disease activity. Patients with the lowest gestation age and birth weight had an increased chance of having the active form of the disease, which required a prompt treatment. The treatment of ROP included laser photocoagulation, intravitreal anti-VEGF therapy and vitrectomy. Anti-VEGF therapy used at the time was bevacizumab. Thus, it is important to recognize the main risk factors and to perform more frequent follow-ups in these children.The strength of this study is that there are no studies in Bosnia and Herzegovina that have investigated gestation age and birth weight as a predictive factor for the development of the active form of ROP and, overall, there is a small number of studies investigating the development of strabismus in these patients. The limitation of this study is a low number of patients, especially in the group with the active form of the disease. The study was conducted in one Clinical Center and can be improved by uniting the data from one more Clinical Center in Bosnia and Herzegovina that treated ROP. One more improvement could be made by comparing both refractive errors and strabismus with these variables. A control group of the same number of full-term children investigated in a prospective manner could increase the significance of this whole research.Strabismus has the higher prevalence in prematurely born children. This study provided proof that there is a correlation of strabismus with the level of prematurity and that both gestation age and birth weight could be used as a predictor for both the development of the active form of the disease and the strabismus diagnosis, especially esotropia. If diagnosed on time, the treatment for strabismus and amblyopia prevention could be performed when needed and therefore could provide a better vision and a better quality of life. Conflicts of Interest statementThe authors declare that there are no conflicts of interest. Informed Consent and Human and Animal Rights statementInformed consent has been obtained from the patient included in this study. Authorization for the use of human subjectEthical approval: The case report related to human use complies with all the relevant national regulations, institutional policies, is in accordance with the tenets of the Helsinki Declaration, and has been approved by the review board of the Veneto Eye Bank Foundation, Venice, Italy. AcknowledgmentsNone. Sources of FundingNone.Financial Disclosure(s)None.


What are the effects of a smartphone-based preterm birth education program in early pregnancy on recommended parental preterm birth knowledge, preparation for decision-making, and parental anxiety?In a parallel-group randomized clinical trial of 120 pregnant participants with a risk factor for preterm birth, those assigned to the smartphone preterm birth video education program (intervention group) had more knowledge of core competencies and were more prepared to make decisions that affect maternal and infant health, without experiencing increased anxiety, compared with participants assigned to the control group.Anticipatory preterm birth education in early pregnancy may empower parents with known preterm birth risk factors to participate in medical care decisions in the event of preterm birth. Preterm birth is a leading cause of infant mortality and child morbidity. Preterm birth is not always unexpected, yet standard prenatal care does not offer anticipatory education to parents at risk of delivering preterm, which leaves parents unprepared to make health care choices during the pregnancy that can improve survival and decrease morbidity in case of preterm birth.To evaluate the effect of the Preemie Prep for Parents (P3) program on maternal knowledge of preterm birth, preparation for decision-making, and anxiety.Recruitment for this randomized clinical trial conducted at a US academic medical center took place from February 3, 2020, to April 12, 2021. A total of 120 pregnant persons with a risk factor for preterm birth were enrolled between 16 and 21 weeks’ gestational age and followed up through pregnancy completion.Starting at 18 weeks’ gestational age, P3 program participants received links delivered via text message to 51 gestational age–specific short animated videos. Control participants received links to patient education webpages from the American College of Obstetricians and Gynecologists.At 25 weeks’ gestation, scores on the Parent Prematurity Knowledge Questionnaire (scored as percent correct), Preparation for Decision Making Scale (scored 0-100), and Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety computerized adaptive test. Analysis was based on an intention to treat.P < .001). Participants in the P3 group reported being significantly more prepared than did participants in the control group for neonatal resuscitation decision-making at 25 weeks . There was no difference between the P3 group and the control group in anxiety at 25 weeks .A total of 120 pregnant participants  were included in the study; 60 participants were randomized to each group. Participants in the P3 group scored higher than those in the control group on knowledge of long-term outcomes at 25 weeks (88.5% vs 73.2%; estimated difference, 15.3 percentage points; 95% CI, 8.3-22.5 percentage points; In this randomized clinical trial, pregnant persons randomly assigned to the P3 program had more knowledge of core competencies and were more prepared to make decisions that affect maternal and infant health, without experiencing worse anxiety. Mobile antenatal preterm birth education may provide a unique benefit to parents with preterm birth risk factors.NCT04093492ClinicalTrials.gov Identifier:  This randomized clinical trial evaluates the effect of the Preemie Prep for Parents program on parental knowledge of preterm birth, preparation for decision-making, and parent anxiety. Half of the 500 000 US mothers who deliver preterm infants receive diagnoses of risk factors months before the delivery,9 yet education on preterm birth and medical decision-making is not consistently provided to them until the delivery hospitalization10 due to clinicians’ concern that it will increase parental anxiety.11A term pregnancy is 40 weeks’ gestational age (GA), and birth at or before 36 weeks’ GA is considered preterm.9 To bridge this gap in prenatal education and support wider dissemination of information to parents at high risk, we developed a multimedia educational aid, the Preemie Prep for Parents (P3) program, in collaboration with parents of preterm infants and perinatal clinicians and based on published guidelines.14 Smartphone-based education allows for learning in small increments at a time and place that suits the patient. Short, animated videos have broad appeal16 and educational efficacy among patients with lower health literacy.17 Moreover, previous work has found higher anxiety among patients hospitalized for preterm labor18 but also found that targeted education reduces anxiety.19 Thus, we hypothesized that, compared with static patient education webpages (control), the P3 program would improve recommended parental preterm birth knowledge, improve preparation for decision-making, and would not increase parental anxiety.Providing preterm birth education during the delivery hospitalization, when the pregnancy is ending, misses the opportunity to influence pregnancy outcomes. It does not allow the family time to contemplate and discuss the presented information, especially for resuscitation decision-making for extremely premature infants.CONSORT) reporting guideline.This was a parallel-group randomized clinical trial conducted at an academic medical center near Milwaukee, Wisconsin. All participants received standard prenatal care. The intervention group received the P3 program, and the control group received links to patient education webpages. This study was approved by the Medical College of Wisconsin institutional review board, and all participants gave written informed consent. As pregnant minors act as decision-makers through pregnancy and preterm birth, we had institutional review board approval to enroll pregnant minors aged 13 to 17 years without additional parental consent , with professional voice actors providing narration , American Academy of Pediatrics (AAP), and American College of Obstetricians and Gynecologists (ACOG).arration . Additioarration . The vidThe control group was provided links by email or text message to patient education webpages created by the ACOG. These publicly available webpages featured information about frequently asked questions on preterm labor, extremely preterm birth, cesarean birth, and a partner’s guide to pregnancy.Study recruitment occurred in person from February 3 to March 13, 2020, and, due to the COVID-19 pandemic, by telephone from April 6, 2020, to April 12, 2021. Pregnant persons aged 13 years or older with a risk factor for preterm birth were approached prior to a prenatal appointment at a maternal-fetal medicine clinic and enrolled between 16 weeks plus 0 days’ GA and 21 weeks plus 6 days’ GA. Risk factors included a short cervix, multifetal gestation, history of spontaneous preterm birth, preeclampsia (at ≤34 weeks’ GA), chronic hypertension, diabetes requiring medications, and intrauterine growth restriction. Those unable to speak English and pregnancies with significant birth defects were excluded. Participants were followed up through pregnancy completion. Final data were collected in July 2021.20 participants completed an enrollment questionnaire and were randomized 1:1 to the P3 (intervention) or control group. To ensure balanced groups in GA at the time of enrollment, randomization was stratified into 2 blocks: 16 to 18 weeks’ GA and 19 to 21 weeks’ GA. The randomization list was generated using the R package blockrand  and implemented through REDCap. Participants randomized between 16 and 18 weeks’ GA began receiving text messages at 18 weeks’ GA, and participants randomized between 19 and 21 weeks’ GA began receiving text messages at enrollment. Participants in the P3 group were sent 0 to 2 text messages per day (schedule dependent on GA at enrollment), which linked to the GA-specific videos. Participants in the control group received an email or text message, depending on their preference, with links to 6 ACOG webpages. We collected clinical data from the medical record regarding the GA at delivery.After consent in Research Electronic Data Capture (REDCap),21 an 11-item measure of confidence in one’s abilities to participate in decision-making; the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety Computerized Adaptive Testing (CAT),22 which measures general anxiety over the past 7 days; the PROMIS Global-10,23 a global assessment of physical, mental, and social health; and the Brief Health Literacy Screen.25 For PROMIS measures, scores were converted to a normed T score, where a mean (SD) of 50 (10) corresponds to the US general population mean.The self-administered baseline assessment included de novo items on sociodemographic characteristics, perceived likelihood of preterm birth, preference for involvement in medical decisions, and typical smartphone use. Race and ethnicity were self-reported using National Institutes of Health–specified racial and ethnic categories. Scores of several previously validated scales were also collected: the Decision Self-Efficacy Scale,26 It is designed to be customized to a particular decision: at 25 weeks, we asked about resuscitation decisions for periviable birth; at 30 weeks, we asked about a risk-appropriate choice of birth hospital; and at 34 weeks, we asked about the decision to breastfeed. We developed the PPKQ to measure the core competencies needed to participate in decisions about preterm birth. Items were drafted by a multidisciplinary team of experts , with content selected based on SMFM-, AAP-, and ACOG-recommended information. Items regarding resuscitation decisions were concordant with the policies of the hospital system from which participants were recruited. Items were evaluated in conjunction with the video usability testing and iteratively refined in multiple rounds of cognitive interviews with diverse parents.28 The PPKQ includes an overall score and 8 subscale scores representing knowledge in the SMFM-, AAP-, and ACOG-recommended domains: (1) long-term outcomes, (2) variability in due date estimation, (3) general prematurity knowledge, (4) lowest GA needed for survival, (5) factors influencing preterm birth outcome, (6) treatment options, (7) short-term outcomes, and (8) advocacy. The long-term outcomes subscale of the PPKQ was selected as the primary outcome because parent knowledge of long-term outcomes is often worse than short-term outcomes19 despite the centrality of long-term outcomes in periviable decision-making.29 The PPKQ can be scored as a sum or percentage correct. The 25-week instrument is available . The Preparation for Decision Making Scale is a 10-item measure of how well a decision aid prepared someone to communicate with clinicians about a health care decision. It has been shown to discriminate between patients who did and patients who did not find a decision aid helpful, with a difference of 12 points on a 100-point scale and SD of 20.Tracking software was developed to record participant use of the P3 program. The software tracked the videos sent, the links participants clicked, the videos played, and the time played for each viewing.We powered the study based on an expected mean (SD) of 50% (35%) correct on the PPKQ long-term outcomes subscale in the control group at 25 weeks. With power of 80% and α of .05, we needed 50 participants in each group to detect a 20% difference in knowledge scores for the P3 group. To allow for attrition and preterm deliveries, we enrolled 120 pregnant participants.We conducted blinded analysis with masked group assignment in the data set. Mean (SD) values were used to summarize continuous variables, while counts and percentages were used for categorical variables. The prespecified intention-to-treat analysis used linear regression to compare pregnant participants in the 2 study groups on PPKQ long-term outcomes at 25 weeks while adjusting for GA at enrollment. Analysis of secondary outcomes was not adjusted for stratification. We used all available data without imputing missing values. We used linear regression to examine associations between knowledge and P3 use captured by the tracking software. All statistical tests were 2-sided; statistical analyses were conducted using SAS, version 9.4 (SAS Institute Inc).We enrolled 120 pregnant patients , with 60 randomly assigned to each group . One parThere were no differences in the baseline characteristics of participants by study group , indicatParticipants in the P3 group watched a mean (SD) of 54.9% (35.1%) of the videos over the 16-week intervention , supporting our primary hypothesis. Considering the PPKQ total score, pregnant participants in the P3 group scored higher than the control group at all 3 time points .Compared with the control group, participants in the P3 group reported more preparedness for a neonatal resuscitation decision at 25 weeks , for choosing an appropriate birth hospital at 30 weeks , and for a decision to breastfeed at 34 weeks  .There were no differences between the P3 and control groups in anxiety at baseline or any subsequent time point  . FurtherAt 34 weeks’ GA, participants in the P3 group were more likely than those in the control group to report that the study materials gave them more information than their physician on premature infants  and on premature labor and delivery . Although most participants in both groups reported that the study materials led them to ask more questions at their prenatal visits , pregnant participants in the P3 group were more likely to report that they discussed preterm birth issues with their partner . The groups were similar with respect to creating a plan for preterm labor .To our knowledge, this is the first parallel-group randomized clinical trial of preterm birth education in early pregnancy for pregnant persons with risk factors for preterm birth. Compared with a control group receiving ACOG webpage links, participants randomly assigned to the P3 program were more knowledgeable about preterm birth at key time points during pregnancy . The P3 participants also reported greater preparedness for making decisions about neonatal resuscitation, birth hospital choice, and breastfeeding. This intervention did not increase participant anxiety.10 because of clinicians’ uncertainty in predicting preterm birth,30 concerns of elevating maternal anxiety,11 and anticipated disinterest in learning until preterm birth is imminent.31 The P3 program seems able to overcome these perceived obstacles. First, our study’s risk factors identified a sample of pregnant persons whose rate of preterm birth (38.7%) was nearly 4 times greater than the general US population rate (10%),32 indicating that our identified risk factors estimated preterm birth well and minimized unnecessary exposure. Second, at each follow-up point, anxiety levels were no different from baseline, and the P3 group did not have greater anxiety than the control group. The mean anxiety T scores at enrollment for both groups were higher than the US general population mean, which is in line with other studies reporting higher-than-average levels of anxiety among pregnant persons during the COVID-19 pandemic.33 Finally, most pregnant participants used at least half the videos despite preterm birth not being imminent. The P3 program has always been accessible and self-paced; for this randomized clinical trial, we further enhanced the curricula by developing high-quality animations, which have been shown to have broad appeal16 and educational efficacy among users with lower health literacy.17 The short, dynamic videos were likely more engaging than static website links, leading to a high level of engagement among participants.Prematurity guidance is typically not offered during routine prenatal care for patients with risk factors19 Although knowledge is not itself behavior change, increased knowledge has corresponded to improvement in self-management for other health concerns, such as diabetes34 and heart disease.35 Similarly, prenatal education for typical pregnancy has demonstrated improvements in identification of true labor, partner involvement, and maternal anxiety.36 Educational aids have been shown to improve patient knowledge and are best suited for preference-sensitive decisions, which include neonatal resuscitation during the periviable period.37 Higher levels of patient knowledge have been associated with more realistic perceptions about treatment options, more active patient participation in decision-making, and increased concordance between patient values and treatment choices.41Participants receiving the P3 program knew more of the information that is recommended by the SMFM, AAP, and ACOG for parents at risk for preterm birth. They also knew more about the potential long-term outcomes associated with preterm birth, which is key information for decision-making that often gets overlooked during traditional counseling.43 The increased awareness of choice and the treatment options, as offered by the P3 program, may lead to greater readiness to participate in shared decision-making for these choices.43In addition to greater knowledge, the P3 program led to more preparedness for decisions that have implications for maternal and infant health. Pregnant participants in the P3 group felt more prepared to discuss decisions regarding neonatal resuscitation, choosing a risk-appropriate birth hospital, and the decision to breastfeed. Conversations between patients and clinicians in which patients feel informed on perinatal topics typically lead to reductions in decisional conflict and regret.44 demonstrating a reduction in anxiety after education, our intervention targeted a group not yet experiencing a medical threat. Our sample was representative of our clinic’s population but not the larger US general population because most participants held a college degree and were White. Moreover, these subgroups were more likely to use the P3 program. Given the preliminary promise of this intervention, a future trial is needed that is powered to investigate maternal and neonatal health outcomes as well as examine important subgroups most affected by preterm birth.This study has some limitations. The study design—randomized assignment, blinded scoring, and blinded comparison of postintervention recommended knowledge between the P3 and control groups—should produce robust and unbiased results, and our study results demonstrated the P3 program’s ability to improve knowledge and preparedness for key health care decisions. However, we did not assess the program’s effect on actual decisions or health outcomes. Given the comparison of the P3 program to an enhanced standard-of-care control group, we cannot draw conclusions about the specific strengths of the P3 program that caused the improvements in knowledge and preparedness . In addition, we were not given permission by ACOG to track participants’ use of the ACOG materials. Although we found no increase in anxiety among the P3 group, the program also did not decrease parental anxiety. However, unlike previous studiesPreterm birth is a leading cause of neonatal and infant mortality and childhood morbidity and can have a profound effect on families. Standard prenatal care does not offer anticipatory guidance to pregnant persons at risk of delivering preterm, but the P3 program is a novel intervention that can provide this guidance. In this randomized clinical trial, pregnant persons with access to the P3 program had more knowledge of core competencies and were more prepared to make decisions that affect maternal and infant health, without experiencing increased anxiety. Mobile antenatal prematurity education as offered by the P3 program may provide a unique benefit to parents with preterm birth risk factors.


A multiple cystic mass in the liver caused an 11-year-old girl who had a history of contact with animals to be referred to our unit. Abdominal ultrasound performed to investigate an abdominal mass revealed the disease. Physical examination revealed no icterus. There was a noticeable swelling in the right upper abdomen. The patient didn't exhibit any allergy symptoms like rhinitis or an urticarial rash. The liver had several low-density lesions, with the largest being a 12-cm-diameter unilocular hepatic cyst in segments IV, VII, and VIII. Two other unilocular cysts were detected in segments V and VI, which suggested liver hydatid cysts. Under general anesthesia, a syringe was used to aspirate intracystic fluid from the patient's largest unilocular hepatic cyst following liver exposure. The cyst was then opened, the internal capsule was taken out, and 15 minutes of hypertonic saline injection followed. Each cyst underwent a subtotal cystectomy with external draining of the remaining cavity. The residual cyst wall was examined intraoperatively for signs of bile leakage, and any apparent biliary holes were individually sutured in healthy tissue. Pathological analysis of the cyst tissue showed the presence of hydatid disease. The postoperative course was uncomplicated, and the patient had a good recovery following the procedure. Three months of ultrasonographic follow-up were carried out, and there was no sign of recurrence.


Previous studies have examined the optimal mode of breech delivery extensively, but there is a scarcity of publications focusing on the birth injuries of neonates born in breech presentation. This study aimed to examine birth injury in breech deliveries.In this retrospective register-based nationwide cohort study, data on birth injuries in vaginal breech deliveries with singleton live births were compared to cesarean section with breech presentation and cephalic vaginal delivery between 2004 and 2017 in Finland. The data were retrieved from the National Medical Birth Register. Primary outcome variables were severe and mild birth injury. Incidences of birth injuries in different gestational ages and birthweights were calculated in different modes of delivery. Crude odds ratios of risk factors for severe birth injury were analyzed.n = 4344), there were 0.8% of neonates with severe birth injury and 1.5% of neonates with mild birth injury compared to 0.06% and 0.2% in breech cesarean section  and 0.3% and 1.9% in cephalic vaginal delivery . Brachial plexus palsy was the most common type of injury in vaginal breech delivery. Increasing gestational age and birthweight had a stronger effect on the risk for injury among cephalic vaginal deliveries than among vaginal breech deliveries.In vaginal breech delivery (Birth injuries were rare in vaginal breech deliveries. The incidence of severe birth injury was two times higher in vaginal breech delivery compared to cephalic vaginal delivery. Brachial plexus palsy was the most common type of injury in vaginal breech delivery.The online version contains supplementary material available at 10.1007/s00404-022-06772-1. Approximately two to three percent of neonates diagnosed with birth injury , 2 are aThe risk for birth injury in breech presentation is considered comparable to that of cephalic vaginal delivery  , 8, as t+0 weeks of gestation with breech presentation was higher after an attempt of VD than after planned CS in two large population-based studies [The incidence of morbidity and mortality of neonates after 37 studies , 10 and  studies . Similar studies , 12. Nev studies , 14 and  studies –17.A considerable amount of literature has been published on morbidity and mortality rates, whereas only a few studies have focused on birth injuries among neonates born in breech presentation. Since the incidence of birth injuries has been described to be relatively low, a large nationwide register was chosen as a study cohort. This study aims to examine the type and rate of birth injuries in vaginal breech deliveries (breech VD) compared to CS with breech presentation (breech CS) and cephalic vaginal deliveries  in Finland, where breech VD in selected women is still a common practice. We also aim to describe the incidence of birth injuries in different gestational weeks and explore the risk factors involved, especially those associated with severe birth injury in different types of delivery.This nationwide population-based cohort study was conducted using data from the Finnish Medical Birth Register (MBR) and the Care Register for Health Care. Both registers are maintained by the Finnish Institute for Health and Welfare. All Finnish hospitals are required to report clinical data to these national registries. The MBR includes data on pregnancies, deliveries, and information on the health of neonates. The data are completed by information obtained from the Central Population Register and the Cause-of-Death Register. The Care Register for Health Care contains information on patient diagnoses and operations performed during the hospital stay. The coverage and accuracy of these registers have been shown to be excellent , 19.The study period was from 2004 to 2017, and it focused on singleton breech deliveries that resulted in a live birth. Breech VD and breech CS were studied separately. Planned and unplanned CS were analyzed together (breech CS) since birth injuries were infrequent after CS. Neonates with cephalic presentation born by spontaneous vaginal delivery or vacuum-assisted delivery formed a cephalic VD group, which was used for comparison. Forceps deliveries were excluded as they were rare , and the presentation of the neonate could not be reliably defined in all cases. Figure +0 weeks of gestation: Breech VD is an option if the mother is motivated to vaginal delivery, the estimated fetal weight is < 4000 g, and the fetus is in a frank, complete, or incomplete breech position with the head in a flexed position during the delivery. Often, adequate measurements of the maternal pelvis are confirmed by magnetic resonance pelvimetry. CS is preferred if intrauterine growth restriction is suspected, or the fetus is otherwise at high risk for distress during delivery. According to national guidelines for preterm deliveries, CS may lower the risk for morbidity in primiparas before 32 gestational weeks [In Finland, five universities with medical faculties offer the education of medical doctors and trainees in gynecology and obstetrics. The management of breech delivery is included in the curriculum of gynecology and obstetrics. There are no national guidelines for term breech pregnancies. However, according to an inquiry addressed to the tertiary level obstetrics centers in Finland, there are common well-established clinical practices for managing breech pregnancies and deliveries after 37al weeks . HoweverThe two primary outcome variables were severe and mild birth injury. Birth injuries detected during the early neonatal period (0 to 6 days) were coded with the Finnish implementation of the 10th Revision of International Statistical Classification of Diseases and Related Health Problems (ICD-10) codes and retrieved from the MBR. In addition, hospital visits linked to any birth injury diagnosis recorded in the Care Register for Health Care during the first year after birth were included to increase the coverage. Severe birth injury was defined according to Muraca et al.  and incl2) were included after 2006, as values from several hospitals were missing for the years 2004 and 2005. Birthweight above + 2 standard deviations (SD) or below − 2 SDs were defined as large for gestational age and small for gestational age standardized for parity, sex, and gestational age in a Finnish population [Tables pulation . The uset-test and Mann–Whitney U-test were used for comparisons of continuous variables.The incidences of severe and mild birth injury were calculated and stratified by gestational age. Variables were described as frequencies and proportions for categorical variables, and as means and standard deviations or medians and interquartile ranges for continuous variables. Welch two sample The risk factors for severe birth injury were calculated. The results are presented as odds ratios and risk differences with 95% confidence intervals (CI). Poisson regression model was used to assess the incidences of birthweight and gestational age using the number of cases per gestational weeks/birthweight as an offset term. The model was used separately for mild and severe birth injuries and in different modes of delivery. Regression analysis was limited to birthweight < 4000 g, as the clinical practice in Finland mainly recommend breech VD when the estimated fetal weight is < 4000 g. Statistical analysis was performed using R Statistical Software version 4.0.3.In total, 650,528 neonates were included. Of these, 4344 neonates (0.7%) had breech VD, 16,979 neonates (2.6%) had breech CS, and 629,182 neonates (96.7%) had cephalic VD, either spontaneous (90%) or vacuum-assisted (10%)  and 40+2 (interquartile range 39+2–41+1), respectively (Table The birthweight of neonates with severe birth injury was 3320 g (SD 483) in the breech VD group and 4071 g (SD 518) in the cephalic VD group. Gestational ages were similar in both groups, 40+0 and 27+6 41% (51/124), 28+0 and 31+6 29% (55/187), 32+0 and 36+6 30% (500/1654), 37+0 and 40+6 19% , and 41+0 and 42+6 30% (402/1344) of fetuses with breech presentation had VD. There were no severe birth injuries, and three neonates (at 31 weeks of gestation) in the breech VD group had a mild birth injury between 24+0 and 31+6 weeks of gestation. In the cephalic VD group, there was a similar finding of single injuries. After 32 weeks of gestation, the incidence of injury remained stable with some sporadic fluctuation up to 42 weeks of gestation among the breech VD group  or the incidence of severe birth injury and gestational weeks . In contrast, the incidence of birth injury showed an increasing trend with higher gestational age in the cephalic VD group , Fig. Between gestational weeks 24Furthermore, no association was found in Poisson regression between birthweight 500 g to 4000 g) and incidence of mild birth injury  or between birthweight and severe birth injury  in breech VD. In the cephalic VD group, the incidence of mild birth injury  and the incidence of severe birth injury  showed an increasing trend along with higher birthweight. In the breech CS group, however, the incidence of mild birth injury seemed to show a decreasing trend with increasing birthweight  Fig. . There w000 g andIn this population-based study, the incidence of severe birth injury was higher in the vaginal breech delivery group than in the cesarean section with breech presentation group and the cephalic vaginal delivery group. However, the incidence remained low in all groups. A brachial plexus palsy was the most frequent injury in vaginal breech delivery. Perhaps because of the more rigorous selection of women for vaginal delivery, high birthweight did not seem to be as important a risk factor for birth injury in vaginal breech delivery as in cephalic vaginal delivery.The total incidence of birth injury in breech VD was similar to that previously reported , 9, 11. Risk factors for severe birth injury, mostly representing the risk factors for BPP, found in cephalic VD were comparable to the risk factors reported for BPP in previous studies that mainly concerned neonates in cephalic presentation  . In the The incidence of birth injury was low in all gestational ages in neonates with breech presentation, and no evidence was found of an association between gestational age and birth injury. It has been suggested that CS reduces perinatal morbidity and mortality in preterm breech neonates , 12, 27,Furthermore, the significance of high birthweight remains unclear. The guidelines recommend preferring CS when the estimated birthweight is  > 3800 to 4000 g –30, but This study provides valuable information on the risks associated with breech deliveries. The strength of this study was the nationwide study population and the long study period that enabled us to study rare incidents such as birth injuries. In Finland, reporting to the registers is mandatory, the medical treatment of pregnancies is homogenous even without national guidelines for breech pregnancies, and the rate of breech VD has remained stable during the twenty-first century . Thus, rOur study confirmed that risk for birth injury is low in breech VD and breech CS. Nevertheless, the risk for severe birth injury, specifically BPP, was higher among breech VD than breech CS or cephalic VD. Birth injuries in neonates with breech presentation were sporadic, and no clinically relevant risk factors were found. These findings suggest that careful selection of women is required to ensure safe vaginal breech delivery.Supplementary file1 (PDF 14 KB)Below is the link to the electronic supplementary material.