Several possible causes for this phenomenon have been investigated, including biophysiological adaptation, epigenetic or genetic mechanisms or lifestyle changes. This is the first study to show the effect modification of altitude and parity on the birth weight length ratio (BWLR) in women resident in moderate altitudes compared to a low sea level.; (2) Methods: This population-based study obtained data on altitude , parity , birth weight and length on all births in Austria between 1984 and 2020 from birth certificates provided by Statistics Austria. The BWLR was calculated, and the effect of moderate altitude and parity was estimated using multivariable linear mixed models adjusting for predefined variables. Sub-group regression analyses were conducted by altitude group. (3) Results: Data on 2,057,702 newborns from 1,280,272 mothers were analyzed. The effect of parity on BWLR, as indicated by the difference of BWLR between the first- and second-born infants, ranged between 1.87 to 2.09 g per centimeter across all altitude groups. Our analyses found that the effect of parity on BWLR diminished from parity three onwards at altitude 0–300, whilst the effect of parity on BWLR continued to increase at higher than 300 m and was most notable in the highest altitude group >900 m. (4) Conclusions: Findings from our study indicated that the negative effect of increasing altitude on BWLR was deprived for newborns of higher parity. It shows that the residential altitude can modify the effect of parity on BWLR. Low birth weight and fetal growth retardation are associated with higher risks of morbidity and mortality in newborns . In addiAltitude is not only described to have an influence on birth weight but also on fetal length. As asymmetric growth describes the different increases in head circumference and abdominal circumference, the birth weight/length ratio serves as a valid predictor for neonatal outcomes ,13. EvidData comprise all birth certificates in Austria between 1984 and 2020 (Statistics Austria) and has been described in detail previously . All datAltitude, in meters (m), was determined by the centroid of the municipality according to mothers’ living addresses. Birth weight was measured in grams. Birth weight was recorded in intervals of 100 g, 10 g, and 1 g from 1984 to 1998, from 1999 to 2010 and from 2011 onwards, respectively. Birth length was measured in centimeters (cm).The following information was used to define inclusion criteria: Austrian citizenship of the mother, maternal age 15–50 years, live birth, gestational age 30 to 44 weeks, birth weight >1000 g, single birth and parity between 1 and 9.The final analysis included mothers whose living address  remained the same over the observation period. This approach avoided cross-over effects when mothers giving birth to more than one newborn moved between altitude levels.The birth weight/length ratio (BWLR in g/cm) was calculated. The effect of altitude on BWLR was estimated using multivariable linear mixed models in SAS (procedure HPMIXED) adjusting for the following variables: education of mother , sex, altitude of residence (kilometers), gestational age (weeks), gestational age squared, maternal age (years), year of birth of the newborn and parity . Parity 8 and 9 were grouped into one single category in order to maintain a sufficient number of observations within each parity group. Newborns of parity 10 and more were excluded because of too few cases.An indicator for the mother was entered as a random effect with an autoregressive correlation term of the first order.p < 0.001). Therefore, we re-ran the regression model within each sub-group of altitude categories  to estimate the effect of parity on BWLR in dependence of altitude. Altitude in meters was kept in the sub-group-specific regression analysis as a continuous variable to avoid residual confounding.In the first step, the interaction between altitude and parity was tested and turned out to be highly significant . All analyses were performed using SAS 9.4 .The study was approved by the Ethics Committee of the Medical University of Vienna and complied with the principles outlined in the Declaration of Helsinki of 1975, as revised in 2013. Participants’ written consent was not required per the Austrian Federal Act concerning the Protection of Personal Data (DSG 2000). All individual data were de-identified before analyses.A total of 2,231,866 observations initially entered the analysis, from which 174,164 observations (8.4%) were removed because mothers moved between altitude levels. Therewith, 2,057,702 newborns from 1,280,272 women remained in the analysis. The mean altitude of mothers’ residential addresses was 430 m  and a minimum of 120 m and a maximum of 1666 m for the whole study population. Overall, 37.2% of the first newborns were delivered at the lowest altitude group (0–300 m), 3.8% at the highest altitude (>900 m) see , and motThe mean BWLR was 66.1 g/cm . The mean BWLR was 66.45 g/cm  at the lowest altitude (0–300 m) and decreased to 64.59 g/cm  at the highest altitude group (>900 m).The mean BWLR was 64.90 g/cm  for first newborns and increased to 67.35 g/cm  for eighth/ninth newborns see .The results of the regression model can be seen in The BWLR of second-born infants is higher than that of first-born siblings by 1.87 to 2.09 g per centimeter across all altitude sub-groups see . This diDifferences in BWLR compared to first-born infants gradually increases from parity 2 to 8–9 in all altitude groups. For newborns at the lowest altitudes (0–300 m), the increase in BWLR from parity 3 onwards is minimal, indicating the effect of parity stays constant. This is in contrast to all other altitude groups, where notable increases in BWLR between the third and fifth birth were observed, i.e., higher birth order predisposes to a greater difference in BWLR in-between siblings.In particular, the increase in BWLR was observed from parity 3 to 5 and then remained stable in altitude groups 300–500 m and 700–900 m, whereas the increase in BWLR continued from parity 3 up to parity 8–9 in altitude groups 500–700 m and >900 m.It is important to note that the number of newborns per parity decreases in the population, leading to increased uncertainty in the observed effects of parity as indicated by wider 95% confidence intervals. This trend becomes pronounced from parity 6 onwards, limiting the statistical power in comparisons between altitude groups.In the altitude group of 0–300 m, the plot reveals a minimal increase in BWLR for siblings with parity of three or more. However, in all other altitude groups, the BWLR shows a progressive increase as parity increases.Our longitudinal study showed increasing BWLR with increasing parity, particularly among women residing at higher altitudes. The detrimental effect of increasing altitude on BWLR was weakened for newborns of higher parity, and the increase in BWLR for higher parity was considerable for mothers residing at moderate altitudes > 900 m.Asymmetric growth restriction at higher altitudes has been well documented in the literature ,16. NewbThe increase in birth weight with parity has been described for years, where the existing literature only addresses birth weight but not BWLR. Primiparous women are more likely to deliver newborns with lighter birth weight and a higher risk of being small for gestational age (SGA) than multiparous . In geneOur study now demonstrated a positive effect of increasing parity on BWLR in women living at higher compared to lower altitudes.Potential mechanisms leading to the influence of altitude on the parity and BWLR association can only be speculated. The chronic hypoxic situation in pregnant women seems to have an effect on the biomolecular pathways of the placentation. Knowledge of biomolecular pathways in the physiological adaption process of pregnant women in hypoxic environmental conditions can lead us to important information about the pathophysiological changes in placental insufficiency and the development of fetal growth retardation. Insights into these mechanisms subsequently lead to the establishment of new possibilities in the prevention and management of placental insufficiency and following conditions . In viewOur study contributes an important part in the investigations of the effect of moderate altitude on BWLR, owing to the longitudinal study design covering the first and later borns of the same mother. In addition to the study design, our study examined BWLR, which carries higher predictive power regarding perinatal outcome than birth weight alone. The major limitation of our study is the lack of information regarding obstetric characteristics. No data is available on the distribution of maternal or fetal morbidities of pregnant women. In particular, the occurrence of pregnancy-associated hypertensive disorders or gestational diabetes, as well as other metabolic or cardiovascular morbidities, would be potential factors to evaluate possible physiological or pathophysiological pathways. Because the occurrence of lower birth weight is more frequent in fetuses with chromosomal anomalies, the exclusion of pregnancies with fetal chromosomal anomalies would be useful in the evaluation of external effects on BWLR. Finally, information on the personal lifestyles of the pregnant population was not available and thus limited the possibility of investigating whether and how environmental and lifestyle factors may influence the effect of altitude on fetal BWLR.In conclusion, our study adds knowledge by investigating the potential effect modification of altitude on the parity and BWLR association in Austria and shows a stronger effect of parity on BWLR at higher altitudes.


Inflammation and oxidative stress play a key role in the development of bronchopulmonary dysplasia (BPD), possibly contributing to persistent respiratory morbidity after preterm birth. We aimed to assess if inflammatory markers were elevated in exhaled breath condensate (EBC) of infants born very prematurely (< 32 weeks gestation) at 12–16 corrected months of age, and if increased levels were associated with BPD diagnosis and respiratory morbidity.EBC samples and respiratory questionnaires were collected from 15 term-born infants and 33 preterm-born infants, 12 with a neonatal BPD diagnosis. EBC samples were analysed for leukotriene B4 (inflammation) and 8-isoprostane (oxidative stress) concentrations using enzyme-linked immune-assays. Differences between groups were analysed by Kruskal-Wallis Test with post-hoc comparisons, independent samples t-test or Mann-Whitney U test depending on normality of the data.Leukotriene B4 and 8-isoprostane levels were elevated in exhaled breath condensate of preterm-born infants compared to those born at term . Leukotriene B4 and 8-isoprostane levels were independent of BPD diagnosis and respiratory morbidity over the first year of life.Infants born very prematurely exhibit elevated markers of airway neutrophilic inflammation and oxidative stress beyond the first year of life, regardless of a neonatal diagnosis of chronic lung disease or respiratory morbidity during infancy. These findings may have implications for future lung health.N/A.The online version contains supplementary material available at 10.1186/s12887-023-04210-y. Infants born very prematurely (< 32 weeks gestation) are often exposed to pro-inflammatory stimuli prior to and following preterm birth. These pro-inflammatory stimuli include chorioamnionitis, respiratory and systemic infections and lung injury from prolonged mechanical ventilation or oxygen supplementation. Inflammation and oxidative stress play a key role in the development of the chronic lung disease of prematurity, known as bronchopulmonary dysplasia (BPD) –3. IncreSeveral small studies suggest that pulmonary inflammation may persist through childhood –7. SputuWe recently published a new, modified, method to collect exhaled breath condensate in infants . EBC is This study aimed to assess if markers of inflammation and oxidative stress were elevated in the EBC of preterm-born infants compared to those born at term, and to determine if these markers are associated with poorer lung health in the first year of life. It was hypothesised that inflammatory and oxidative stress markers will be increased in EBC collected from preterm-born infants compared to those born at term. It was also hypothesised that increased inflammatory marker levels at 12–16 months are associated with a neonatal diagnosis of BPD, increased neonatal respiratory support and increased respiratory symptoms in the first year of life.Preterm-born infants between 12 and 16 months corrected postnatal age (cPNA) attended Princess Margaret (now known as Perth Children’s) Hospital as part of the Preterm Infant Functional and Clinical Outcome (PIFCO) follow-up study ACTRN12613001062718) . At thei001062718Term-born healthy infants aged between 9 and 18 months were recruited from the community and their study participation involved a home visit. At the home visit, a general health questionnaire was completed by the infant’s parents. EBC was collected during natural sleep during their regular sleep time. Term-born participants were born at or after 37 weeks gestation with no history of wheeze and/or recurrent cough, doctor diagnosis of respiratory disease or any neonatal respiratory disease.Both term- and preterm- born infants were excluded from the study if they had major congenital abnormalities influencing cardiorespiratory function.Written informed consent was received from the parents/guardians of the participants. The PIFCO follow-up study was approved by the Child and Adolescent Health Service (CAHS) HREC [Approval #2014083EP]. Sample analysis was approved by Curtin University (HRE2020-0097). Approval for the recruitment and sample collection from healthy term-born infants was obtained from Curtin University (HRE2018-0407).EBC was collected using an R-Tube collection device  adapted for collection in neonates and infants by reducing dead-space, as previously described by our group . EBC wasSamples were analysed for leukotriene B4 and 8-isoprostane concentrations using enzyme-linked immune-assays (ELISA). Any samples with insufficient volume for both assays were prioritised for 8-isoprostane analysis. ELISA buffer, ELISA standards, samples, AChE tracers and ELISA antiserums for leukotriene B4 and 8-isoprostane were added to the assay plates according to the protocol outlined by the Cayman Chemical Leukotriene B4 EIA Kit  and 8-Isoprostane EIA Kit . A standard curve was plotted using the absorbance readings of the maximum binding, non-specific binding and standard wells. The standard curve was then used to determine the concentrations of leukotriene B4 and 8-isoprostane in the EBC samples. Measures below the limit of detection were assigned a concentration of 0 pg/mL.Normally distributed data are presented as means and standard deviations. Non-normally distributed data are presented as medians and interquartile ranges. To assess differences in demographic and respiratory history data between the term and preterm group, independent samples t-test or Mann-Whitney U test were used depending on normality of the data. Similarly, a sub-analysis was conducted within the preterm group between those with and without BPD. Mann-Whitney U test was used to determine if the concentration of biomarkers was elevated in those born preterm, compared to term. A sub-analysis was conducted using the Kruskal-Wallis Test to examine the differences between the term, preterm with BPD and without BPD groups, with Bonferroni correction for multiple tests. Bivariate correlation (Spearman’s rho) was used to assess associations between biomarker levels and length of neonatal respiratory support, and Mann-Whitney U Tests to determine whether biomarker levels were elevated in the presence/absence of symptoms, hospitalisations, medication usage and respiratory diagnosis. Analysis was performed using SPSS for Windows . A p-valExhaled breath condensate samples were collected from 15 term-born infants (mean age 14.4 ± 2.9 months) and 33 preterm-born infants (mean age 14.4 ± 1.0 months), 12 of whom had a neonatal diagnosis of BPD. Of those with BPD, 7 were classified as moderate/severe BPD. All infant EBC samples were analysed for 8-isoprostane, with enough sample for leukotriene B4 analysis for 9 (60%) term-born participants and 29 (87.9%) preterm-born participants, 9 (75%) with BPD. 3 term infant samples had levels below the limit of detection , these values were imputed as zero. Anthropometric, birth and respiratory history information for infant participants are found in Table Leukotriene B4 and 8-isoprostane levels were elevated in the exhaled breath condensate of preterm-born infants compared to those born at term  , asthma medication use , any respiratory events (such as upper respiratory tract infections (URTI), bronchitis, bronchiolitis, croup, pneumonia)  or hospitalisations for respiratory reasons   have persistent airway inflammation evidenced by elevated leukotriene B4 and 8-isoprostane in EBC of the preterm infants compared to those born at term. No associations were found between biomarker levels and neonatal diagnosis of BPD, increased neonatal respiratory support or increased respiratory symptoms in the first year of life.The increased levels of leukotriene B4, a marker of neutrophilic inflammation , and 8-iThe finding of elevated neutrophilic inflammation markers at 12–16 months in infants born very preterm is concerning. Elevated inflammation causes lung injury and alters development in the neonatal intensive care unit (NICU) period , and airOur study found no direct correlations of biomarker levels with gestational age, neonatal factors or respiratory symptom history, and no difference in biomarker levels between those with and without BPD. The absence of a direct association between EBC biomarkers at 12–16 months and indicators of early life respiratory morbidity may indicate that regardless of BPD diagnosis, preterm-born infants exhibit ongoing lung inflammation and oxidative stress. These findings are similar to those reported by Filippone et al. who found elevated 8-isoprostane in preterm-born adolescents both with and without BPD . HoweverThe lack of correlation with neonatal factors or symptoms may be explained by the inability to normalise EBC for variable dilution of airway surface liquid in water vapour, including by minute ventilation which previous studies have shown is associated with EBC volume in infants . The varTogether, the results of the present study reinforce emerging evidence that neutrophilic inflammatory and oxidative stress processes persist in the airways of survivors of preterm birth regardless of BPD diagnosis. Although inflammatory biomarker levels were not directly associated with indicators of respiratory morbidity in the first year of life in this study, the elevation of these markers in survivors of preterm birth beyond 12 months of age may indicated increased risk of future respiratory morbidity as previously observed in the preterm-born population. Interventions that target neutrophilic inflammatory and oxidative stress processes may be useful in ameliorating the respiratory morbidity observed in survivors of preterm birth. The identification of elevated airway neutrophilic inflammation and oxidative stress at 9–16 months in those born preterm provides some insight into the pathogenesis of long-term respiratory morbidity in this population and identifies potential targets for intervention to preserve lung health in these children.Below is the link to the electronic supplementary material.Supplementary Material 1


Intimate partner violence (IPV) has been associated with an elevated risk of multiple adverse birth outcomes, yet little is known about how specific IPV influences adverse birth outcomes. The aim of this study was to examine the association between IPV during pregnancy and adverse birth outcomes .I2 statistic accompanied by chi-square p-value was used to assess heterogeneity, and funnel plot and Peter's test were used to assess publication bias.Systematic searches were conducted using four databases: EMBASE, Web of Science, PubMed, and CINAHL for observational studies published from 1 January 2011 to 31 August 2021. Two reviewers independently carried out the literature search, study selection, data extraction, assessment of the study, and risk of bias assessment; disagreements were resolved by a third reviewer. A random-effect model was used to calculate the odds ratio (OR) with a 95% confidence interval (CI) for preterm birth, low birth weight, and stillbirth. I2 = 88%), low birth weight , and stillbirth . We attained comparable results among all specific IPV including physical, sexual, emotional, and mixed.In total, 23 studies met the inclusion criterion. IPV was associated with preterm birth (OR = 1.84; 95% CI: 1.37–2.49; Intimate partner violence and specific IPV during pregnancy were significantly associated with adverse birth outcomes, especially for physical IPV. An urgent need for greater action to prevent or intervene in IPV during pregnancy is warranted.https://www.crd.york.ac.uk/prospero/.CRD42021282936,  Intimate partner violence (IPV) is a major and common public health problem in society globally . IPV refPrevious studies have explored the associations between IPV and adverse birth outcomes including preterm birth, low birth weight, and stillbirth , 5. The Various types of IPV have been associated with adverse birth outcomes, including physical and sexual IPV . PreviouWe conducted a comprehensive and rigorous meta-analysis to explore the association between IPV and adverse birth outcomes. Our main aims were to: (1) evaluate the association between IPV during pregnancy and three adverse birth outcomes: preterm birth, low birth weight, and stillbirth, which were leading causes of neonatal morbidity and mortality; (2) explore the relation of specific types of IPV with adverse birth outcomes.The review included studies reported on IPV during pregnancy considering every pregnant woman as a population. The exposure to IPV was defined as experiencing any physical, sexual, or emotional abuse perpetrated by a current or former partner. We defined women who experienced more than one type of IPV at the same time as mixed IPV in the present study. Women who reported not experiencing IPV were considered as a control in this review. The outcome of the review included preterm birth, low birth weight, and stillbirth. Preterm birth refers to a baby born before 37 weeks of gestation, whereas a low birth weight is referring to a baby born with a weight of < 2,500 grams. A stillbirth is defined as a baby dying after 28 weeks of pregnancy but before or during delivery.In this review, all quantitative observational studies reported on the relationship between IPV during pregnancy and the outcomes of interest were included. Meanwhile, the articles included in the present study had to meet the following criteria: (1) English language; (2) published in/after 1 January 2011; (3) raw data included. However, observational studies that did not report on original research  or just qualitative studies were excluded.We searched four databases including EMBASE, Web of Science, PubMed, and CINAHL from 1 January 2011 to 31 August 2021. We planned to summarize contemporary literature through this review, thus, the included studies were limited to the past 10 years, considering that the birth outcomes may be influenced by environmental, behavioral, and sociodemographic factors –15. In aThis systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . We haveTwo independent reviewers (Guo and Wan) searched for articles that met the inclusion criteria, obtained potentially relevant articles through a preliminary screening of the titles and abstracts, and then read the full text of the literature and determined its eligibility through the exclusion criteria. For any discrepancies, a third reviewer (Ge) was consulted, and we would reach a consensus. Then, two reviewers (Guo and Wan) independently extracted the data from the eligible studies using a pre-prepared form. Extracted data were reviewed and verified by the reviewer (Ge). The form mainly included study characteristics , type of IPV  and the abuse assessment tool, and the adverse birth outcomes .We critically appraised all included studies using the Joanna Briggs Institute (JBI) checklist for cross-sectional studies, the JBI checklist for cohort studies, and the JBI checklist for case–control studies . BrieflyI2 statistic accompanied by a chi-square p-value. Heterogeneity was assigned adjectives of low, moderate, and high to I2 values of 25, 50, and 75% (I2 ≥ 50%). The aforementioned analyses were based on the year of publication (as a continuous variable), development level (developed countries and developing countries), study quality (continuous), and measurement of IPV (self-report questionnaires and face-to-face interviews). All analyses were conducted in RStudio-4.0 using the meta package.We calculated the odds ratio (OR) with a corresponding 95% confidence interval (CI) for preterm birth, low birth weight, and stillbirth using a random-effect model, which is suitable where there is heterogeneity between included studies. Heterogeneity across studies was assessed using an  and 75% . Publica and 75% . We usedA total of 1,403 articles were identified through the four databases. After removing the duplicates and preliminary screening titles and abstracts, 73 studies were selected and read in full text to assess the eligibility along with five studies identified from the references lists. Ultimately, 23 studies were included, meeting the aforementioned inclusion and exclusion criteria, and providing the raw data that needed to be included in the meta-analysis .WHO Domestic Violence Questionnaire, eight studies), and five studies were obtained through face-to-face interviews with doctors or nurses in hospitals. The majority of studies focused on physical IPV and single birth outcomes, mostly preterm as a birth outcome.As demonstrated in I2 = 88%, p < 0.01). Based on 13 studies, the pooled OR for IPV associated with low birth weight was 2.73 (95% CI: 1.66–4.48) and heterogeneity is 95% (p < 0.01) (I2 = 64%) (As shown in  < 0.01) . As for 2 = 64%) .I2 = 97%), sexual IPV , emotional IPV , and mixed IPV . For the low birth weight, the ORs for the association of the specific IPV  were, respectively, 3.69 (95% CI: 1.51–9.02), 2.64 (95% CI: 1.44–4.82), 2.12 (95% CI: 1.08–4.15), and 2.11 (95% CI: 1.54–2.90) (As shown in 54–2.90) .p-value > 0.05). The details are shown in Visual inspection of the funnel plots for preterm birth, low birth weight, and stillbirth showed little publication bias . Peter'sThe aim of the present study is to synthesize the recent studies involving the association between IPV during pregnancy and adverse birth outcomes. At the global scale, all subtypes of IPV were associated with an increased risk of adverse birth outcomes, especially for physical IPV. To evaluate the robustness of our findings, we calculated the association in different subgroups, including the development level, study quality, and measurement of IPV.Consistent with previous studies, we found that IPV is a risk factor that can lead to severe birth outcomes involving preterm birth, low birth weight, and stillbirth , 44. DonThis study evaluated the association between IPV during pregnancy and preterm birth, low birth weight, and stillbirth and showed that IPV during pregnancy can not only harm the pregnant woman herself but also adversely affect the birth outcomes, which can more intuitively present the severity of IPV during pregnancy, so as to alert the health decision-makers and healthcare providers to its attention. The proportion of eligible birth outcomes is also an indicator of a country's socioeconomic development. Therefore, based on the results of this study and reality, we are likely to put forward a proposal; women who experience IPV during pregnancy should be identified as early as possible and given care and support to avoid more serious physical and emotional damage and worse birth outcomes. Prenatal care can be an important entry point for identifying violence among pregnant women, as under normal circumstances most people receive at least one or more prenatal care visits. Paradoxically, prenatal care and health services specifically for IPV during pregnancy are not available in almost all countries. IPV raises many ethical and legal issues, and to prevent and intervene in IPV during pregnancy, we must collaborate between healthcare, political, and social justice systems.This meta-analysis has several strengths including considering stillbirth as an adverse birth outcome in our study. Although prior meta-analyses existed, none included stillbirth as an interesting outcome , 52, 53.This meta-analysis summarized all literature on the association between IPV during pregnancy and adverse birth outcomes in the last decade. Women who experienced IPV during pregnancy had a higher risk of adverse birth outcomes when compared to women who have not been exposed to IPV during pregnancy. All specific IPV, including physical, sexual, emotional, and mixed, were associated with adverse birth outcomes. In the future, more research on IPV during pregnancy is warranted and there is also an urgent need for greater action to prevent or intervene in IPV during pregnancy.The original contributions presented in the study are included in the article/FG and JZ were responsible for the study's concept and design. CG and MW independently extracted the data. FG reviewed and verified extracted data. CG, MW, PW, and FG cleaned the data and performed the analyses. CG, MW, YW, MT-P, and FG drafted the article. All authors contributed to the interpretation of data. All authors read and approved the final manuscript.


Prematurity is associated with increased risk for morbidity and mortality. Aim of this study was to evaluate whether cerebral oxygenation during fetal-to-neonatal transition period was associated with long-term outcome in very preterm neonates.2) and cerebral fractional tissue oxygen extraction (cFTOE) within the first 15 min after birth were analysed retrospectively. Arterial oxygen saturation (SpO2) and heart rate (HR) were measured with pulse oximetry. Long-term outcome was assessed at two years using “Bayley Scales of Infant Development” (BSID-II/III). Included preterm neonates were stratified into two groups: adverse outcome group  or favorable outcome group (BSID-III > 70). As the association between gestational age and long-term outcome is well known, correction for gestational age might disguise the potential association between crSO2 and neurodevelopmental impairment. Therefore, due to an explorative approach the two groups were compared without correction for gestational age.Preterm neonates ≤ 32 weeks of gestation and/or ≤ 1500 g with measurements of cerebral regional oxygen saturation (crSO(p = 0.009*) and 1250 g (972–1390) (p = 0.001*) in the favorable outcome group, respectively. crSO2 was lower (significant in 10 out of 14 min) and cFTOE higher in adverse outcome group. There were no difference in SpO2, HR and fraction of inspired oxygen (FiO2), except for FiO2 in minute 11, with higher FiO2 in the adverse outcome group.Forty-two preterm neonates were included: adverse outcome group n = 13; favorable outcome group n = 29. Median(IQR) gestational age and birth weight were 24.8 weeks (24.2–29.8) and 760 g (670–1054) in adverse outcome group and 30.6 weeks (28.1–32.0) 2 during immediate fetal-to-neonatal transition when compared to preterm neonates with age appropriate outcome. Lower gestational age in the adverse outcome group would suggest beside lower crSO2 also lower SpO2 and HR in this group, which were however similar in both groups.Preterm neonates with adverse outcome had beside lower gestational age also a lower crSOThe online version contains supplementary material available at 10.1186/s12887-023-03960-z. Prematurity is associated with higher risk of adverse short- and long-term outcome, including cerebral palsy with a rate between 5 and 10% and a mortality rate of 10–15% in high-income countries . Short-t2), measured by near-infrared spectroscopy (NIRS) already during immediate fetal-to-neonatal transition compared to neonates without IVH [2 and cerebral fractional tissue oxygen extraction (cFTOE) values before the development of severe peri-/intraventricular haemorrhages with a decrease in crSO2 values afterwards.Premature birth is also associated with poor long-term outcome including impaired neuro-development, visual disorder and increased risk for chronic disease in adulthood . Long-tehout IVH . After thout IVH  observed2 within the first 15 days after birth and long-term outcome, assessed at a corrected age between two to three years using BSID III in preterm neonates. They observed a significant correlation between lower crSO2 within the first 15 days after birth and impaired cognitive development. Alderliesten et al. investigated whether high and low levels of crSO2 measured during the first 72 h after birth were associated with adverse long-term outcome in preterm neonates. An association between crSO2 values less than 55% within the first three days after birth and neurodevelopmental impairement has been described [2 during the fetal-to-neonatal transition to guide respiratory support reduces the burden of cerebral hypoxia in preterm neonates [Verhagen et al.  investigescribed . Pichlerneonates .2 and cFTOE during the fetal-to-neonatal transition, within the first 15 min after birth, are associated with poor long-term outcome  at a corrected age of two years, evaluated by Bayley Scales of Infant and Toddler. Secondary aim was to analyse in addition short-term outcome at term-equivalent age/ time-point of discharge home. We hypothesise that lower crSO2  within the first 15 min after birth were associated with impaired neurodevelopment.Hence, the primary aim of the present study was to evaluate whether differences in crSOA retrospective explorative single-center study was performed at the Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria. This study was approved by the Regional Committee on Biomedical Research Ethics (EC number: 33–561 ex 20/21) and was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) . Data ofIn the present retrospective analysis, preterm neonates with a gestational age ≤ 32 weeks and/or a birth weight ≤ 1500 g and available long-term outcome data were included. Data of long-term neurodevelopmental outcome included a clinical examination and, in addition, a Bayley Scales of Infant and Toddler Development (BSID) at a corrected age of two years, if feasible. Furthermore, included preterm neonates of this present retrospective study, had to be included in former prospective NIRS studies with measurements of cerebral oxygenation within the first 15 min after birth and with decision to conduct full life support according to the local guidelines. In the present retrospective analysis, we excluded preterm neonates if less than 50% of cerebral NIRS data during the first 15 min after birth were available, those with severe congenital malformations and those with lost to follow-up.BSID was assessed at a corrected age of two years by trained assessors (psychologists). From 2010 to 2013 the BSID II and from 2014 to 2018 the BSID III were used. The results of the BSID II were converted to the cognitive scale assessed by BSID III using the following formula : BSID IIThe included preterm neonates were stratified into two groups according to their long-term outcome at a corrected age of two years. Preterm neonates who died or survived with severe disability were stratified to the adverse outcome group. Severe disability was defined as a cognitive BSID III score ≤ 70 or the inability to perform BSID III testing due to severe cognitive disability. Preterm neonates who survived without severe disability, defined as cognitive BSID III scores > 70, were stratified to the favorable outcome group.2 and cFTOE) measured with NIRS during the first 15 min after birth. Secondary outcome parameters were mortality  and short-term morbidity at term-equivalent age/ time-point of discharge home. Morbidities were cerebral injuries , pulmonary morbidities , abdominal morbidities , need for abdominal surgery), ROP and sepsis. Cerebral injuries, any grades of IVH and/or cystic PVL, were assessed by routinely performed cerebral ultrasound. BPD was defined as oxygen dependency or need of respiratory support at 36 weeks corrected age. NEC needing surgical intervention and any grade of ROP were documented. Provided medication  and respiratory support  during initial resuscitation and provided medication  and respiratory support  during the hospital stay were assessed and analysed.The primary outcome parameter was cerebral oxygenation (crSO2) and was calculated out of SpO2 and crSO2 for each minute: cFTOE = (SpO2-crSO2)/SpO2, providing information on the oxygen extraction of the tissue in dependence of SpO2.The antepartum medical history and demographic data  of the preterm neonates were documented. A stopwatch was started when the neonate was fully delivered. Cord clamping was routinely delayed for 30 s after birth. Immediately after the cord was clamped, the preterm neonate was placed under an overhead heater in supine position, dried, wrapped in warm towels and/or plastic bags according to gestational age. Initial postnatal resuscitation, respiratory support  and cardio-pulmonary resuscitation were performed according to the latest guidelines , 17. Pro2 and HR were monitored non-invasively using pulse oximetry  applied on the right hand or wrist. Mean arterial blood pressure in minute 15 after birth was measured using a neonatal pneumatic cuff, applied on the left upper arm . All variables were stored continuously during the first 15 min after birth in a multichannel system  for subsequent analysis. SpO2 and HR values were stored every second, whereby the sample rate of crSO2 was 8 s (0.13 Hz).SpO2, cFTOE, SpO2, HR, and fraction of inspired oxygen (FiO2) were investigated in an explorative sense within the first 15 min after birth using linear mixed model with a first-order autoregressive covariance structure with fixed effect time and group. For visualization of the results, estimated means and 95% confidence intervals for the means are presented. Post hoc analysis of differences between groups for each minute were performed. P-value < 0.05 was considered statistically significant.The patients were divided in two groups, based on their long-term outcome. Patient characteristics are presented ad median (IQR) or n (%) and compared between groups using t-test or Mann-Whitney- U-test for continuous variables and chi-square test or Fisher’s exact test for categorical variables. Courses of crSODue to the retreospective analyses in an explorative way and due to the expected low sample size no correction for multiple testing and mulitvariate regression analyses were planned. Statistical analysis was performed using the software SPSS 26.0 .Between March 2010 and June 2018, 88 preterm neonates with a gestational age of ≤ 32 weeks and/or a birth weight ≤ 1500 g were included in the above described prospective NIRS studies. In eighteen preterm neonates less than 50% of NIRS data were available and we, therefore, excluded them from further analysis. One further preterm neonate had to be excluded due to a severe cerebral malformation. Twenty-seven preterm neonates were excluded, as no long-term outcome data due to a lost to follow-up were available. Thus, a total of 42 preterm neonates, with a presence of cerebral NIRS measurements and BSID testing at a corrected age of two years, were included in our retrospective analysis. Thirteen neonates had an adverse outcome (death or severe disability) and were allocated to the adverse outcome group. Twentynine neonates were allocated to the favorable outcome group according their long-term outcome , amniotic infection , preterm labour , amniotic sac prolapse , multiples , placental abruption , pathological CTG , and intrauterine growth restriction .Causes for preterm birth were pre-eclampsia . In both groups, the preterm neonates were appropriate for age. One neonate in the adverse outcome group received chest compressions, but none of the neonates received catecholamines during the first 15 min after birth.Demographic and clinical data of the included preterm neonates are presented in Table In the adverse outcome group five preterm neonates died (38%). Two suffered from severe cerebral haemorrhage, in both cases IVH III and PVH. One preterm neonate died due to severe respiratory insufficiency as a result of severe lung hypoplasia. One preterm neonate died six months after birth due to severe BPD . One preterm neonate died due to multi-organ dysfunction syndrome including NEC, IVH and ultimately cardiac arrest.Short-term outcome parameters at age-equivalent age and/or discharge home are presented in Table (p < 0.001*). The results of BSID III motor scale was 79 ± 10 in the adverse outcome group and 97 ± 10 in the favorable outcome group, respectively (p = 0.014*).Long-term outcome was assessed at a median (IQR) of 24 (24–24) months of corrected age in both groups in the surviving neonates. Three preterm neonates in the adverse outcome group survived with severe cognitive disability, rendering BSID II/III testing impossible. Cerebral palsy occurred in two patients in the adverse outcome group. Thus, in the adverse outcome group only five neonates were capable for BSID II/III testing. In the favorable outcome group all preterm neonates were tested with BSID II/III. Mean ± SD of cognitive BSID II/III was 61 ± 8 in the adverse outcome group and 105 ± 16 in the favorable outcome group, respectively 2 and cFTOE during the first 15 min, starting in minute two, after birth are displayed in Table 2 was lower in the adverse outcome group compared to the favorable outcome group (p = 0.010*). Post hoc analysis of crSO2 for each minute showed significant differences for almost all minutes (10 out of 14 min). In contrast, cFTOE was higher in the adverse outcome group compared to the favorable outcome group (p = 0.003*). Post hoc analysis also showed significant differences for almost all minutes (11 out of 14 min).The courses of crSO2, HR and FiO2 during the first 15 min after birth, starting in minute two after birth, are displayed in Fig. 2(p = 0.361) and HR (p = 0.595) did not differ significantly between groups. There were no differences in the provided FiO2 between the two groups (p = 0.128). Nevertheless, in the post-hoc analysis a significantly higher FiO2 was seen in the adverse outcome group compared to the favorable outcome group at minute 11.The courses of routine monitoring parameters SpO2 values and significantly higher cFTOE values, with no differences in SpO2 and HR during fetal-to-neonatal transition in the adverse outcome group. The preterm neonates in the adverse outcome group were also more immature and had more short-term morbidities compared to the favorable outcome group.This is the first study, which investigated a potential association between cerebral oxygenation during the first 15 min after birth and long-term outcome in preterm neonates. We observed significantly lower crSOLower gestational age is well known to be associated with a higher rate of adverse short-term and long-term outcome , 2. This2 and consequetively in cFTOE between the two groups in the first minutes after birth, with significantly lower crSO2 values indicating prolonged cerebral hypoxia in the adverse outcome group. As we observed significant differences in crSO2 without differences in other routine vital parameters we assume that the additional harm of cerebral hypxoia during immediate fetal-to-neonatal transition may play an important role on long-term outcome.In the present study we demonstrated that although no differences in routine vital parameters were observed, there were significant differences in crSO2 values during the first 72 h after birth and showed that crSO2 was lower in more immature preterm neonates. Gestational age dependent crSO2 values in preterm neonates during the first 15 min after birth have not been described yet, although, it seems very likely, that in this early postnatal period, crSO2 values might be lower in more immature preterm neonates, too. However, it seems difficult to differentiate causal and associative relationships of crSO2 in regard to gestational age. The present study at least may point out an additional impact of impaired cerebral oxygenation during fetal-to-neonatal transition on neurodevelopmental outcome. Furthermore, this present study, display a new approach, as no correction for gestational age was performed. As lower gestational age is already known to have a crucial influence on long-term outcome, an association between gestational age and long-term outcome is very likely. Therefore, a correction for gestational age might disguise the potential causality between lower crSO2 during fetal-to-neonatal transition and neurodevelopemental long-term outcome. The importance of adequate arterial and regional oxygenation during during fetal-to-neonatal transition is still a matter of intense discussion. Hence, there are recommended SpO2 targets within the resuscitation guidelines [2 targets > 80% at 5 min after birth. Not reaching the target was associated with increased risk of IVH and death. In our study, SpO2 was similar in both groups, whereby neonates in both groups had a mean SpO2 of less than 80% at minute five after birth. Although there was no difference in SpO2 values between our two groups, there were differences in neurodevelopmental outcome. To define cerebral hypoxia two concepts were followed, either defining an absolute threshold value after the immediate transition [2 for each minute during fetal-to-neonatal transition [2 centile were significantly more pronounced in neonates, who developed an IVH compared to preterm neonates without the occurrence of IVH. The influence of cerebral hypoxia on short-term neurological outcome, assessed with GMA, has been described by Pansy et al. [Alderliesten et al.  observedidelines , 17, 19.idelines  reportedansition  or definansition . A post-ansition . In contansition  and Fuchansition  observedy et al. . They ob2 was < 10th percentile [2 values of both groups. Again, we would like to emphasize, that there were no differences in SpO2 and HR between the two groups. Furthermore, preterm neonates in the adverse outcome group had, except for one minute, no differences in supplemental oxygen during immediate resuscitation, leading to the hypothesis that routine monitoring parameters alone are not sufficient to display cerebral oxygen demand necessary for an age-appropriate neurodevelopment.In the present study, crSOrcentile  in the aNevertheless, given our present findings we have to assume that cerebral hypoxia within the first minutes after birth may have an attributive impact on long-term outcome in preterm neonates. We, therefore, assume that preterm neonates with lower cerebral oxygenation during fetal-to-neonatal transition, are in a higher risk for an impaired short-term and long-term outcome.Besides cerebral oxygenation, there may be several factors with a negative impact on long-term neurodevelopmental outcome in preterm neonates, including prolonged mechanical ventilation, co-morbidities and systemic steroid exposure –28. Howe2, whereby without knowing which parameter might be primarily causative.There were several limitations of our study. First, the number of analysed preterm neonates with impaired long-term outcome was quite low and the number of neonates lost to follow-up was quite high and might have induced a bias. It may be assumed that preterm neonates with favorable outcome are more likely to be lost to follow-up compared to preterm neonates with obviously impaired neurodevelopment. Nevertheless, even with this small cohort the differences especially in cerebral oxygenation during the first minutes after birth were rather pronounced. A multivariate analysis was not feasible due to the sample size. However, in the present study adverse outcome is described to be associated with low gestational age and low crSOSecond, no data of magnetic resonance imaging or electroencephalograms were available, which might have provided further information on our patients’ short- and long-term outcome. Third, using BSID for stratification has some limitations itself. BSID III provide the risk for underestimation of developmental delays, which might have an influence on our results. Nevertheless, BSID is currently the most widely used standardized developmental tool for early diagnosis of developmental delays. Furthermore, there exist cut-off points for mild, moderate and severe developmental delay. The cut-off point in the present study was the widely used for severe disability , 36. The2 and higher cFTOE during fetal-to-neonatal transition, compared to the favorable outcome group, whilst there were no significant differences in the routine monitoring parameters SpO2 and HR. There were also no differences in provided FiO2 between the two groups, except for one minute. The present reults suggest that lower cerebral oxygenation during fetal-to-neonatal transition might play an important role as an influencing factor on long-term outcome.Preterm neonates with adverse long-term outcome had beside a lower gestational age lower crSOFurther prospective studies are warranted, investigating the possible association between cerebral oxygenation during fetal-to-neonatal transition and long-term outcome especially in very and extremely preterm neonates.Below is the link to the electronic supplementary material.Supplementary Material 1


Prolonged farrowing and more piglets born with low birth weight are undesirable consequences of genetic selection for increased litter size. The objective of the present observational study was to evaluate the relationship between piglets’ survivability and farrowing kinetics in hyperprolific sows. A total of 58 sows of different parities and 1190 piglets were included. The entire farrowing process was monitored and the following parameters were recorded: inter-piglet birth interval, birth order, total born, live born, dead born, and mummified piglets, obstetric intervention, weight at birth and 24h, colostrum yield and intake.p < 0.05) with parity, number of stillborn and mummified piglets. Piglet mortality 24h after birth was negatively affected (p < 0.01) by birth weight and positively affected (p < 0.01) by cumulative birth interval. The last tercile of piglets born (birth order ≥ 17) had the highest (p < 0.01) inter-piglet birth interval (IPBI) (43.4 ± 4.17 min) compared to piglets born in the first (birth order between 2 and 7) (26.5 ± 3.8 min) and second (birth order between 8 and 16) terciles (21.9 ± 3.8 min). Cumulative birth interval, birth weight, occurrence of stillborn piglets and manual intervention were positively associated (p < 0.05) with IPBI. Piglet birth weight was also positively associated (p < 0.01) to individual colostrum intake. Piglets ingesting more colostrum had lower (p < 0.01) mortality from 24h after birth until weaning. Sow’s parity and cumulative birth interval were positively associated with the presence of stillborn piglets .The sows included in this study had on average 20.6 ± 0.6 total piglets born, of which 16.4 ± 0.6 were live born, 3.3 ± 0.4 were stillborn and 0.9 ± 0.2 were mummified piglets. The average farrowing duration and average birth interval were 411.3 ± 31.6 and 20.6 ± 1.7 min, respectively. Farrowing duration was positively associated (Reducing farrowing duration may be crucial to decrease stillbirth rate and neonatal mortality in hyperprolific sows. Moreover, special care must be provided to the lighter piglets within a litter to increase their colostrum intake and minimize piglet’s mortality throughout lactation.The online version contains supplementary material available at 10.1186/s40813-023-00332-y. Prolonged farrowing > 300 min) and high inter-piglet birth interval (IPBI) (> 20 min) are arguably the most important factors leading to both increased stillbirth rate and increased preweaning mortality observed in modern hyperprolific sows i.e. sows giving birth to more than 16 piglets, compared to older genotypes 00 min an. Others Piglets with greater birth order show more signs of asphyxia such as higher lactate concentration and lower blood pH compared to piglets born in the beginning of farrowing –8. ConseThe positive association between farrowing duration and stillbirth rate is however more consistent. According to Tummaruk et al. , sows wiProlonged farrowing might not only lead to an increased stillbirth rate, it may also negatively affect the vitality, colostrum intake, growth, and survivability throughout lactation , 7. PeriElucidating the variables interconnecting farrowing kinetics and piglets’ survivability is an essential first step to minimize perinatal losses. Therefore, the aim of the present observational study was to investigate the relationship between piglets’ survivability and farrowing kinetics in hyperprolific sows.All descriptive data of the sows, the farrowing process and the litter performance are shown in Table All the results obtained from univariable or multivariable regression models are summarized in an overview table Table .Table 2Sp < 0.01) IPBI compared to piglets born in the first and second tercile  as shown in Fig. p < 0.05) than the IPBI of the birth order 4 to 16, but it did not differ from the IPBI of the birth order 2, 3 and 17 to 23  with IPBI. It was estimated that an increase of one minute in cumulative birth interval increases 0.08 ± 0.01 min in IPBI and an increase of one kilogram in piglet’s birth weight increases IPBI in 6.25 ± 4.0 min . In a multivariable model considering binary variables as independent variables affecting IPBI, the occurrence of both stillborn and manual intervention were also positively associated (p < 0.01) with IPBI, increasing it in 18.68 ± 3.26 and 98.03 ± 5.71 min, respectively.The multivariable regression model considering IPBI as dependent variable is summarized in Tables p = 0.02, p = 0.01 and p = 0.03, respectively) variables  with average colostrum intake per piglet. Each extra liveborn piglet was associated with an average decrease of 13.3 ± 2.1 g of colostrum per piglet, and an increase in 0.1ºC in the sow’s rectal temperature was associated with an average decrease of 79.1 ± 24.5 g of colostrum per piglet. Birth weight was positively associated (p < 0.01) with individual colostrum intake per piglet (Table The multivariable regression model considering average colostrum intake by piglet per sow as dependent variable is summarized in Table p < 0.01) with piglet’s birth weight and cumulative birth interval, as shown in Table p < 0.01) variable associated with piglet mortality from 24h post-farrowing until weaning  with the presence of a stillborn piglet.The probability of piglet’s survival during farrowing decreased as the cumulative birth interval increased Fig. . The mulOnly piglets born alive (0) and stillborn piglets (1) were included in this analysis (1152 piglets). Mummified piglets were excluded.In the present study, piglets born in the last tercile of birth order had higher IPBI compared to piglets born in the first and second terciles. This result agrees with another result from the present study where a positive linear association was found between cumulative birth interval and IPBI. These results together allow the interpretation that as the farrowing progresses, the piglet-piglet interval increases and, hence, the last piglets born are more prone to suffer from the detrimental effects of hypoxia. Van Dijk et al.  found a It is estimated that sows’ energy requirement on the day of farrowing is 1.6 times higher compared to late gestation, mainly because of colostrum production, physical activity related to nest-building behavior, and the labor during farrowing . CollectPiglet’s birth weight was also associated with longer IPBI. This finding has already been demonstrated in Large White x Meishan  and in DThe positive association between parity and farrowing duration found in the present study agrees with other studies , 28. It th piglet born), interventions may be considered even in the beginning or middle of the farrowing to avoid the cumulative effect of IPBI and cumulative farrowing duration on the risk of stillbirth occurrence.The present study showed a positive association between stillborn piglets and farrowing kinetics, which agrees with several other studies , 31, 32.Although a cumulative effect of IPBI and farrowing duration may occur, the effect of farrowing duration seems to be more deleterious to piglets’ survivability since cumulative birth interval and not IPBI was associated with stillbirth occurrence and piglets’ mortality 24h after farrowing. In agreement, Langendijk et al.  showed tNeonatal mortality is a major cause of pre-weaning losses and the first 24h after birth are the most critical period , accountImpaired piglet’s colostrum intake may also be attributed to sow-related factors , 44. AltThe average piglet’s colostrum intake was also negatively associated with the sow’s rectal temperature 24 h after farrowing. An increase in rectal temperature is the earliest clinical sign to predict exacerbated inflammatory response during peripartum in sows , 48. It The time elapsed from the onset of farrowing (expulsion of the first piglet) until the birth of a given piglet  emerged as one of the most important factors influencing piglet survivability during and 24h post farrowing in hyperprolific genotypes. Although less relevant to piglets’ survivability, the IPBI may also increase the stillbirth rate, especially when acting together with cumulative birth interval. Therefore, strategies to decrease the farrowing duration of modern sows without impairing piglet’s vitality and maternal health must be developed. Moreover, older sows should be more carefully monitored during farrowing and obstetric interventions must be considered in sows showing evidence of dystocia.The study protocol was approved by the Ethical Committee of the Faculty of Veterinary Medicine and the Faculty of Bioscience Engineering, Ghent University (EC2019-26), as well as by the Flemish governmental agency for animal welfare (DWZ/ER/20/1.15/).The study was performed in a commercial farrow-to-finish farm with an average herd size of 500 DanBred sows (Landrace x Yorkshire) and practicing a 4-week batch production system. Piglets were weaned at 21 days of age. Sows and gilts were transferred to the farrowing unit three to seven days before the expected farrowing date where they were housed in conventional farrowing crates until weaning. Prior to moving them to the farrowing unit, the animals were fed a gestation diet. After arrival in the farrowing unit, they received a transition diet until two to three days after the last sow had farrowed. From then onwards until weaning, sows were fed with lactation diet. The precise composition of the different feeds can be found in Schoos et al. . All theSows and gilts that farrowed prior to gestation day 115 and after day 117 (considering the first insemination day as day 0 of pregnancy) were not considered for the study. Induction of farrowing was not applied. Cross-fostering and split suckling were allowed only after 24h after the onset of the farrowing.The backfat thickness was considered as the average of measurements performed in the left and right side of the sows at the P2 position  at the entrance in the farrowing room, farrowing day, and weaning. The rectal temperature was daily assessed between 9 and 11 a.m. from the day of entrance in the farrowing unit until seven days after the last sow had farrowed.Total born, live born, stillborn and mummified piglets were recorded. The average birth interval was calculated by dividing the farrowing duration by the number of total born piglets in the litter. The IPBI was calculated as the time elapsed between the birth of a piglet and the birth of the next piglet. The cumulative interval was calculated as the time elapsed between the onset of farrowing (expulsion of the first piglet) and the birth of a piglet.At birth, piglets were weighed and received an individual ear tag, and 24h (23–25 h) later, the piglets were weighed again to estimate colostrum intake and colostrum yield. Colostrum intake was estimated based on the mechanistic model as described by Theil et al. . If the p < 0.05. Statistical analyses were performed using software R .The assumption of normality and homogeneity of variances were graphically evaluated  and tested by Shapiro–Wilk and Barlett, respectively. When needed, dependent variables were transformed in order to meet the assumptions of the statistical model used. The data were presented as mean ± SEM and the results were considered significant at The birth order was categorized into three groups to analyze the IPBI according to the piglet’s expulsion, with 25 being the maximum birth order as the number of piglets from birth order 26 onwards was too low to fit the model adequately. The number of piglets born in each birth order is in Additional File p < 0.05 were included in the final model. The elimination of independent variables in the stepwise procedure was performed according to the p-value; independent variables with higher p-values were eliminated earlier. The complete linear regression models, including inclusion and exclusion criteria and stepwise procedure are shown in Additional File Univariable models were used to investigate the association between predicted and predictor variables, where each explanatory variable was included as a single fixed effect. Numerical and categorical independent variables with p ≤ 0.20 for the F-test in the simple model were selected and subjected to Pearson’s and Spearman’s correlation analysis to avoid multicollinearity between continuous variables and confounding problems between categorical variables. Based on the results from the univariable models, all factors with p ≤ 0.20 were included as independent variables in a multivariable analysis. After a stepwise elimination procedure, only independent variables with Statistical models that had the dependent variable as a binary variable  were analyzed by generalized linear mixed models fitted by binomial distribution.Sow was considered as a random variable in statistical models that analyzed dependent variables at the piglet level .Interaction between the variables included in the final model was tested and found to be non-significant for all models.Survival analysis (Kaplan–Meier estimate) was performed using the “survival” package and “survfit” function with a confidence interval of 95%.Additional file 1. Supplementary Tables.


Male pelvic cyst rarely causes symptoms; here, we are presenting a case of a 48-year-old gentleman who presented with acute urinary retention stemming from a pelvic cyst. This presentation has been recurrent despite undergoing repeated TRUS aspiration of the cyst to relieve the symptoms. We performed a robotic pelvic cyst excision with peritoneal window in an attempt to cure the patient. Based on the MRI and histopathology, it was likely a seminal vesicle cyst that is causing these recurrent episodes. On 3 months follow-up, the patient was symptom free without any complaints. He complained of progressive obstructive lower urinary tract symptoms of weak stream, dysuria, and suprapubic pain. The patient did have a history of transrectal ultrasound guided (TRUS) aspiration of a seminal vesicle cyst before one year. The physical examination was unremarkable apart from digital rectal examination that showed large soft mass compressing the rectum, which hindered the assessment of the prostate. A magnetic resonance imaging (MRI) was performed which showed a pelvic cystic lesion, displacing the urinary bladder and prostate anteriorly and the rectum posteriorly, measuring 13× 9 x 9.5 cm, along with solid component that appears contiguous with enlarged transition zone of the prostate. The right and left seminal vesicles were identified along lateral margin of the cystic lesion on each side 3MRI and supported by histopathology reports.Male pelvic cysts (MPC) are considered to be a rare entity, with a prevalence of 1–5%.Symptoms of MPC vary from asymptomatic to irritative or obstructive LUTS, infertility, chronic pelvic pain syndrome, painful ejaculation, or hematospermia.Diagnosis of MPC is usually incidental.The treatment of MPC revolves around decompression of the cyst. This could be done by TRUS guided aspiration, transurethral deroofing, and open or laparoscopic surgeries for cyst excision with risk of recurrence.4Although rare, large pelvic cysts causing recurrent obstruction can result in a significant burden on patient's quality of life and health. The choice of treatment modality depends on the presentation, location, and size of the cyst, in a step wise approach starting from TRUS aspiration up to robotic excision.The authors declare that they have no financial or non-financial conflicts of interest related to the subject matter or materials discussed in the manuscript.


Ventricular rupture with pseudoaneurysm is a rare phenomenon that usually occurs after myocardial infarction, previous cardiac surgery and infectious or inflammatory conditions. To prevent rupture of the pseudoaneurysm, urgent repair is recommended. We report successful open surgical repair of a 46-year-old man, who presented with pseudoaneurysm communicating with left ventricle. Left ventricular (LV) pseudoaneurysm is a rare condition that forms after ruptured ventricle is contained by pericardium or scar tissue . While fA 46-year-old man from rural Ethiopia was referred 7 days after he started to have sudden shortness of breath, chest pain and cough. On 6th day of his symptoms, he had brief loss of consciousness and left-sided body weakness. When he arrived to our hospital on 7th day of symptom onset, his vitals were: blood pressure 100/70 mmHg, pulse rate 104–112 beat/min, respiratory rate 24 breaths/min, SpO2 95% on room air. There was Grade 3 systolic murmur at the apex. Power of left upper and lower extremities was 3 and 4 out of 5, respectively. Laboratory tests were white cell count of 15 800, with 89% neutrophils, hemoglobin of 11.4 g/dl, platelet count of 180 000, INR of 2.2. Cardiac markers and Electrocardiogram (ECG) were normal. Echocardiography showed 19 mm defect at apex of left ventricle with bidirectional flow between ventricular chamber and pseudoaneurysmal septated intrapericardial collection. Chest CT revealed huge pseudoaneurysm (contained rupture) the communicates with left ventricle via a 2.1 cm rupture see  and 2. PWith diagnosis of embolic stroke and LV pseudoaneurysm, he was stabilized in cardiac intensive care unit, and then operated via median sternotomy. Pericardium appeared edematous and darkened because of underlying hematomata. To prevent uncontrolled bleeding, extrapericardial cannulation was done on ascending aorta. Then pericardium covering right atrium was then opened and superior vena cava was cannulated and bypass was initiated. When pericardium over the pseudoaneurysm was then opened, there was a huge cavity measuring about 16 cm transverse and 10 cm vertically, which had pushed the heart upward. There was some thrombus inside. It was freely communicating with inferior wall of LV close to apex through a 2 cm rupture. The cavity wall and coagulated hematoma were removed and perforation repaired with Dacron patch see . Chest tIn the largest review of case reports of LV pseudoaneurysm that included 290 patients, the most common causes of LV pseudoaneurysm formation were myocardial infarction (55%), previous cardiac surgery 33%) and trauma (7%) . In the 3% and trLV pseudoaneurysms mostly present with symptoms; however, about 10% may be asymptomatic , 6. MurmWorkup should include ECG and echocardiography. In setting MI-associated pseudoaneurysm, about 95% have abnormal ECG, mostly nonspecific ST changes . TransthEven though true natural history of LV pseudoaneurysm is difficult to determine because of publication bias, surgery offers better outcome than medical treatment alone. Surgery is a recommended treatment of choice as LV pseudoaneurysms have high risk of rupture 30–45%) and mortality of about 48% with medical treatment alone , 8. Surg% and morLV pseudoaneurysm occurs when ruptured ventricle is contained with scar tissue or pericardium. It is usually a complication of myocardial infarction, however, it can occur in patients without evidence of myocardial infarction, especially if they present late when myocardial markers might be negative. It is prone to rupture, and the rupture site should be repaired under cardiopulmonary bypass with pledgeted suture or graft. Caution must be taken not to enter pseudoaneurysm cavity before cannulation, which otherwise could lead to uncontrolled bleeding.


The incidence of congenital abnormalities is highest in low-and-middle-income countries. However, the prevalence, spectrum, trends of neonatal congenital anomalies and their admission outcomes have not been well explored. This study was a 10 year retrospective hospital-based research in a low-income country to address the above.All infants hospitalized in the Special Care Baby Unit at the Cape Coast Teaching Hospital in Ghana, between 1st January 2010 and 31st December 2019, had their demographic, obstetric, and clinical data recorded.. Health center/clinic delivery proffered a better survival than hospital delivery, but this should be interpreted with caution.Over the decade, 236 neonates with congenital abnormalities were admitted to the unit, accounting for 2.8% of total neonatal admissions and 8.6 per 1000 births. Mortality occurred in 33.2% of neonates with congenital abnormalities, corresponding to 4.6% of all neonatal deaths. Mortality was significantly associated with place of delivery and gravidity of more than five. The commonest anomalies were in the nervous system, particularly neural tube defects, followed by suspected chromosomal abnormalities and then cardiac defects. Neonates with cardiac defects had a higher chance of dyingNeural tube defects were the most predominant anomalies; hence, intensification of preconception and antenatal folic acid supplementation is pivotal towards their reduction. Making prenatal screening for early detection of fetal anomalies an integral part of routine antenatal care is also essential. This research was conducted in a single center and did not include stillbirths and abortions so cannot give an accurate estimation of the number of congenital abnormalities in the population. A national registry of congenital anomalies is recommended. What is already known? It is known that congenital abnormalities or birth defects contribute significantly to under-five mortality and their incidence in LMICs forms about 94% of the global cases. Despite this high burden, there is a general lack of epidemiological data on the prevalence, pattern, and outcomes of congenital anomalies in Ghana and other LMICs.What this study adds? This study provides a large database of data on neonatal congenital abnormalities and is the first to report on the prevalence and spectrum of congenital abnormalities in the Central Region of Ghana. The trend of neonatal abnormalities that warrant admission and their admission outcomes have also been explored for the first time in the country. The World Health Organization (WHO) defines congenital disorders as “any potential pathological conditions arising before birth, whether evident at birth or manifesting later in life” (WHO). They are also referred to as birth defects, congenital malformations, congenital anomalies, or congenital disorders. The commonest of these defects are the structural  abnormalities Czeizel, . Birth dCongenital abnormalities in LMICs account for 94% of the total global number of congenital abnormalities and are among the top five causes of the under-five mortalities  as its facilities are not up to a standard neonatal intensive care unit as the highest level of mechanical ventilation offered is continuous positive airway pressure. The Paediatric ward admits older infants and stable neonates who have been de-escalated from the SCBU. Paediatric surgery services are limited in the hospital. A visiting pediatric surgeon runs an outpatient clinic and performs surgeries every two weeks. Neurosurgery and pediatric urology services also begun in CCTH after 2015. Because of the lack of a pediatric cardiologist and cardiac surgery services in the hospital, all cardiac cases are referred to the leading public tertiary hospital in the country, which is in the capital city in another region. Infants who need urgent care by the pediatric surgeon on days outside his visiting times, and infants who require intensive care services are also referred to the same hospital. All live infants with congenital anomalies, whether delivered in the hospital or referred in, are examined at the SCBU for a management plan. Neonatal autopsies are not routinely performed unless requested by the clinicians or parents of the infant.Stillbirths with congenital defects were excluded from this study. Neonates with more than 30% of missing data were also not included.All health records at the SCBU, including the Admissions and Discharges (A&D) book were used to obtain maternal and newborn data. Eligible neonates were entered into an Excel spreadsheet. Data available in the records include gestational age at delivery, place and mode of delivery, date of birth and age in days at the time of admission, sex, birthweight, diagnosis, and maternal’ information such as name, age, and parity. Information on maternal folic acid intake in the index pregnancy, chronic medical illnesses and whether the neonatal defects were diagnosed prenatally are not available in those records. The admission outcome  and the number of days spent on the ward were also recorded. Data was not collected withanonymity, but information was kept private and accessible to only the researchers.Preterm: infants born before 37 weeks gestation,Term: infants delivered at gestational ages between 37 and the 40th week (the expected date of delivery)Postdate: pregnancy that is between 40 and 42 weeks gestationPost-term: pregnancy that has lasted beyond the 42nd weekExtremely low birthweight infant: an infant that weighs < 1000 g at birthVery low birthweight infant: an infant that weights 1000–1499 g at birthLow birthweight infant: an infant that weighs 1500–2499 g at birthNormal birthweight infant: an infant that weighs 2500–3999 g at birthHigh birthweight infant: an infant that weighs ≥ 4000 g at birthHealth Center: the first point of contact between the formal health delivery system and the client. It serves a population of about 20,000 and offers basic curative and preventive services. It is manned by a physician/medical assistant.Clinic: a health facility that does not meet the criteria for a hospital, as defined by the Health Facilities Regulatory Agency  coding system was not employed in this study. The abnormalities were categorized into 13 subclasses using a modified version of the EUROCAT subclassification system . Frequencies, proportions, percentages, mean with standard deviation, median, and charts were used to present descriptive data. The outcome variable was the status of the baby upon exiting from the SCBU or the Paediatric ward . In a univariate analysis, Pearson chi-square was performed to examine the relationship between independent factors and mortality. At 95% confidence level, a p-value of 0.05 was considered statistically significant. The variables with significant p-values in the bivariate analysis were entered into a Cox regression analysis for adjusted hazard ratios. Kaplan–Meier survival graphs were created to compare survival among the various categories of variables that were associated to mortality.During the ten-year period, 8346 neonates were admitted to the SCBU, 236 of whom had at least one congenital abnormality. A total of 1593 neonatal fatalities occurred. As a result, the prevalence of congenital anomalies at the SCBU was 2.8% (236/8346). Over the decade, total deliveries were about 27,320 (both live and stillbirths) in the hospital, giving the SCBU admissions rate in the hospital as 30.5% of total deliveries (305 per 1000 births). The mortality rate for newborns with congenital anomalies was 33.2% (n = 74/227), accounting for 4.6% (74 out of 1593) of all SCBU deaths over a ten-year period.Table Over half of the neonates were delivered vaginally. Majority of the newborns were admitted in SCBU for less than 7 days and nervous system anomalies were the most common congenital anomalies followed by suspected chromosomal anomalies and cardiac defects Table .Table 2MTable Figure The highest number of neonates who died with a diagnosis of congenital anomaly was observed in 2016 followed by 2015 and 2010  survived. This is similar to the observation made in an earlier study in another tertiary care facility in Ghana, which analyzed congenital malformations in the general pediatric population but excluded chromosomal and cardiac defects ; hence, the increasing number of admissions only resulted in greater mortalities in 2015 and 2016, and not 2014 and 2019. The reason for this trend is unclear although it suggests most of the cases during that period were either amenable to surgery or were just not fatal. Due to the unavailability of data on this from other studies, the finding cannot be appropriately situated in the national and global context. Further research is needed to ascertain the factors that accounted for the high mortality rates in those years.The subclasses with the most mortalities were cardiac, multiple, and other anomalies/ syndromes. More than half of neonates with cardiac abnormalities (61.5%) died and all six that had a cyanotic heart disease, demised. This may support the view that there are more cardiac defects in Sub-Saharan Africa that are not amenable to surgery due to their severity  as a strategy to lowering maternal and neonatal mortality. As of 2014, antenatal care and SBA utilization rates were 97% and 76%, respectively  as a major risk factor for death in newborns with congenital abnormalities. Birth order greater than three , suspected chromosomal abnormalities and cardiac defects are the commonest congenital anomalies among hospitalized neonates in the Cape Coast Teaching Hospital. Therefore, preconception and antenatal folic acid supplementation, and prenatal screening should be emphasized repeatedly at the antenatal clinics. Also, it is imperative to improve data collection in the hospital, build a national registry for congenital abnormalities and make them notifiable or reportable to acquire adequate data that can inform policies on their prevention and management.