The aim is to investigate the associations of the mother’s socioeconomic and lifestyle factors and life satisfaction with the delivery of a small for gestational age (SGA) infant.Data from 4598 participants of the population-based birth cohort study Survey of Neonates in Pomerania (SniP) including comprehensive information on pregnancies, mothers, and their offspring in Western Pomerania, Germany were used in this study. The associations were analyzed using linear and logistic regression models.p < 0.01) and smoked more frequently during pregnancy (p < 0.01) compared with mothers of adequate for gestational age (AGA) neonates. A mother with less than 10 years of education and one who continued smoking during pregnancy had an odds ratio (OR) of 2.23 [95% confidence interval (CI) = 1.44 to 3.46] and 2.68 (95% CI = 2.06–3.49) of having an SGA infant, respectively. There was no association between the employment of the mother (p = 0.28), the monthly income (p = 0.09), the family status (p = 0.80), the number of friendships outside the household that the mother would not wish to relinquish (p = 0.47), the number of people that she could rely on in case of an emergency (p = 0.75), or alcohol consumption prior to (p = 0.14) or during the pregnancy (p = 0.99) with SGA. Finally, women who delivered SGA infants were more frequently dissatisfied with their employment (p = 0.03) and financial status (p < 0.01).After logistic regression analysis adjusted for height of the mother, women who delivered SGA infants, had lower education (Women who delivered SGA infants had more associated socioeconomic and lifestyle risk factors and were more frequently dissatisfied with their life conditions than mothers of AGA neonates. A substantial worldwide decline in maternal and neonatal mortality by nearly half has been observed in the last 2 decades –3. This Perinatal mortality is higher in SGA infants compared with neonates born appropriate for gestational age (AGA). This association is present in both term and preterm infants –10. SGA Many factors affect the duration of gestation and fetal growth, and thus, the birth weight. These factors depend on the characteristics of the infant, the mother, or the physical environment and play an important role in determining the future health of the neonate . SGA infThe objective of this study is to analyze the relationships between mothers´ socioeconomic and lifestyle factors, social support and life satisfaction and the delivery of an infant with SGA in a birth cohort in northeastern Germany.n = 1155) or women admitted to the maternity ward who we were unable to contact (n = 401), an anonymous minimum dataset was abstracted comprising data on the health status of the newborn, but without detailed information about environmental parameters. A non-responder analysis revealed no meaningful selection bias , weight gain during pregnancy in kg, number of previous pregnancies and prior pregnancy losses were obtained from the prenatal care booklet. In Germany, every pregnant woman visiting her gynecologist receives a prenatal care booklet where this information is recorded. The maternal place of birth was asked in the face-to-face interview.The maternal age, height, prepregnancy body mass index  of having an SGA infant. While a high proportion of all pregnant women continued smoking during their pregnancies (around 21%), the prevalence of current smoking of the SGA pregnancies was twice as frequent when compared to AGA pregnancies. After logistic regression analysis adjusted for the height of the mother, a mother who continued to smoke during pregnancy had an OR of 2.68 (95% CI = 2.06–3.49) of having an SGA infant. On the other hand, there was no association between the employment or unemployment of the mother before pregnancy , the monthly income , the family status at birth , the number of friendships outside the household that the mother would not wish to relinquish , the number of people that the mother could rely on in case of an emergency  and alcohol consumption before  or during the pregnancy  with the delivery of an SGA infant  and financial status  and with their living situation in general . On the other hand, there were no associations between the mother´s satisfaction with their housing situation , leisure time , health situation , family situation  and relationships with friends, neighbors and acquaintances  and the birth weight for gestational age  and maternal stress during pregnancy in a low-income sample consisting of 77 healthy mother-children pairs . MaternaA study in one hospital in Taiwan  with 198Many factors affect the fetal growth and thus the birth weight for gestational age. They relate to the infant, the mother, and the physical environment and play an important role in determining the future health of the infant . We beliIf a correlation between psychosocial risk factors in pregnant women and birth weight is confirmed, it might be possible to develop screening tools to identify women with increased risk for developing a pregnancy with SGA fetuses and provide the necessary support to avoid this complication.The main strength of this study is the use of a large sample which includes the majority of the births in a specific population over a period of time. Furthermore, we used specific birth weight charts for the analyzed population. This reduces the risk of potential misclassification as birth weight charts influence the classification and incidence of SGA .Study limitations include the difficulty in obtaining valid and reliable data on alcohol intake and smoking during pregnancy. Although this was mitigated by the use of validated questionnaires, the AUDIT-C  and the While previous studies have shown the relative influence of environmental and genetic factors that explain the variation in birth weight, our findings showed an association of maternal lower educational status, smoking and life dissatisfaction with delivery of an SGA infant. Future studies should analyze whether interventions designed to support women exposed to these risk factors might avoid the occurrence of SGA births and their complications.


Positive associations for SEPP1 VC suggest preferential transfer from mother to fetus. We found small associations between infant growth and WBSe VC ); 12 months ). Weight-for-age z-score also showed weak negative associations with delivery WBSe ; 12 -months: −0·05 ) and in WBSe VC ; 12 months: −0·05 ). Given the fine balance between essential nutritional and toxic properties of Se, it is possible that WB and serum Se may negatively impact growth outcomes, both in utero and postpartum.Deficiency of essential trace element, Se, has been implicated in adverse birth outcomes and in child linear growth because of its important role in redox biology and associated antioxidant effects. We used data from a randomised controlled trial conducted among a cohort of pregnant and lactating women in Dhaka, Bangladesh to examine associations between Se biomarkers in whole blood (WBSe), serum and selenoprotein P (SEPP1) in maternal delivery and venous cord (VC) blood. Associations between Se biomarkers, birth weight and infant growth outcomes  at birth, 1 and 2 years of age were examined using regression analyses. WB and serum Se were negatively associated with birth weight (adjusted  Global estimates (most recently from 2019) suggest that over 149 million children under the age of 5 are stunted. According to the 2017–2018 Bangladesh Demographic and Health Survey, indicators of malnutrition among children under 5 years of age declined between 2007 and 2018, with the most recent prevalence estimates for stunting in children at 31 %, 22 % for underweight and 8 % for wasting.Linear growth, an important indicator of a child’s present and future health, is influenced by a complex interaction of environmental factors including intra-uterine growth restriction, household socio-economic status, parental education levels, inadequate maternal and child nutrition and frequent infections. Due to adaptive changes in Se metabolism that occur during pregnancy, requirements are higher given its role in fetal growth, which manifests as lower maternal concentrations of blood Se. Concentrations of this trace element are known to fall during pregnancy, with lowest levels observed at delivery,8. Levels are lower because of increased fetal demands and alterations in intestinal absorption or renal handling,8. Reduced Se concentrations can have an adverse impact on antioxidant selenoproteins, which compromise protection against placental oxidative stress during pregnancy, negatively impacting fetal growth.Se is an essential trace element that is known for its role in redox biology. A recent meta-analysis found that umbilical cord blood Se concentrations  are correlated with birth weight, although similar results were not observed for associations between maternal blood Se and birth weight. Other studies have demonstrated significant relationships between low birth weight (LBW) and lower Se concentrations. Mechanisms for the associations between birth weight and Se remain unclear; however, its antioxidant properties play an important role in placental development and oxidative balance. Lower Se levels are likely associated with reduced function of glutathione peroxidase, an antioxidant enzyme involved in protecting the placenta and fetus from oxidative stress,10. In a similar manner, SEPP1 (selenoprotein P) is a selenoenzyme glycoprotein that protects against adverse pregnancy outcomes which can have an impact on fetal growth,10. Se levels may also be correlated with small-for-gestational age (SGA) status; mechanistically, these associations may function via reductions in glucose levels which subsequently impact fetal weight. Lower placental glutathione peroxidase activity has been observed in women with SGA compared with controls. Due to the effects of lowered Se levels and decreased glutathione peroxidase activity during pregnancy, placental antioxidant defence may be reduced which in turn may impact fetal growth, resulting in adverse birth outcomes including growth restriction and SGA. A comprehensive schematic of placental to fetal transfer of various selenometabolites and Se metabolism in the human body is presented in online Supplementary Fig. 1.Se is known to play a protective role in many birth outcomes–15. Expression of selenoproteins by bone cells can contribute to protection against oxidative stress in the microenvironment of the bone. Se deficiency impacts bone formation and resorption, whereby the effects of Se on bone are mediated through reduced antioxidative capacity, accumulation of reactive oxygen species, reduced osteoclast activation and osteoblast differentiation. Furthermore, Se deficiency is known to impact cartilage and can reduce bone mineral content, as described in human and animal studies,14,16.In addition to the effects of Se on birth weight and birth outcomes, this micronutrient also plays an essential role in bone growth and development. Se inadequacy has been implicated in growth faltering and changes in bone metabolism which can impact bone and cartilage development. SEPP1 is the primary transporter and storage selenoprotein from the liver to bones, where the Lrp8 receptor facilitates SEPP1-mediated Se uptake, particularly under conditions of Se deficiency,18. Se therefore plays an important role in bone physiology and is tightly regulated by SEPP1 receptor, apolipoprotein receptor 2. Expression of this receptor is significantly influenced by SEPP1 levels in a negative feedback loop. Genetic ablation of SEPP1 has been shown to reduce serum Se concentrations by 25-fold but only reduces bone Se levels by 2·5-fold, suggesting a protective effect.Se metabolism and use in the bone are exclusively associated with selenoproteins. A total of nine selenoproteins have been identified in human fetal osteoblasts where they play a role in bone metabolism,9,19. Given the mixed body of evidence on the association of Se with birth weight and infant growth outcomes, we sought to understand whether Se status measured in maternal and infant whole blood (WBSe), serum (serum Se) and a biomarker of functional status, SEPP1, at delivery and in venous cord (VC) blood is correlated with infant birth weight, growth outcomes (length-for-age z-score (LAZ), weight-for-age z-score, weight-for-length z-score and head circumference-for-age z-score) at birth, in infancy and up to 2 years of age. Our study will add to a growing body of evidence on the role Se may play in in utero and postnatal infant growth and development.Studies have examined associations between Se levels in mother–infant dyads and growth outcomes at birth and in the postnatal period3 supplementation during pregnancy and lactation conducted in Dhaka, Bangladesh for this secondary analysis. Details of the parent study (NCT01924013) are described elsewhere. Briefly, a total of 1300 women, 18 years of age and older, with uncomplicated singleton pregnancies were enrolled between 17 and 24 weeks of gestation and randomised into one of five treatment groups .We used observational Se biomarker data collected as part of double-blinded, dose-varying, placebo-controlled, randomised trial of the effect of maternal vitamin D.Exclusion criteria included high risk pregnancies, women who had pre-existing medical conditions or those who were taking medications that could put them at risk of vitamin D sensitivity, altered vitamin D metabolism and hypercalcaemia. Additional details are provided elsewhereInclusion of participant samples for this secondary analysis was based on availability of at least one measurement of Se and/or selenoproteins at delivery in mothers or in VC blood of neonates. Infants for whom length and weight were not measured at birth or 12 months were excluded.. Samples selected for Se quantification were not related to vitamin D treatment group, and seasonal imbalances in specimen collection were observed for those selected to be a part of the sub-study. Additional socio-demographic characteristics of study participants were recorded using standardised data collection forms.Se was measured as part of a panel of metals and minerals for which the primary study intent was to examine effects of vitamin D supplementation on heavy metal concentrationsMaternal and VC blood samples were collected at delivery by trained phlebotomists. Trace metal-free EDTA-coated tubes were used to draw maternal samples, and whole-blood aliquots were drawn prior to centrifugation. Cord blood was collected within 30 min of delivery from a site on the umbilical cord attached to the placenta after wiping maternal blood away with dry gauze. The umbilical vein was cannulated to collect blood into a lavender top EDTA tube. Whole blood was stored at −70°C or colder.. The lower limit of detection for this assay was 24·5 µg/l. Serum Se was measured at delivery using inductively coupled plasma-dynamic reaction cell-MS as described by Caldwell. The lower limit of detection was 4·5 µg/l. No dilution factors were applied for these assays. Plasma SEPP1 was measured at delivery and in VC blood using a Selenotest ELISA colorimetric assay  performed at the Hospital for Sick Children. The lower limit of detection for the assay was 267·3 µg/l, with a 33-fold dilution factor applied and intra and inter-assay CV measured at 4·5 and 10·1 %, respectively. At least one Se biomarker was measured in a sub-sample of 1021 specimens collected from mothers or infants for inclusion in this study.Whole blood and serum Se were measured at the US Centers for Disease Control and Prevention (CDC). WBSe was measured at delivery and in VC blood using inductively coupled plasma MS. In brief, head circumference, length and weight were measured by trained professionals using standardised procedures adapted from the INTERGROWTH-21st  Project. Infant length was measured using a ShorrBoard. Infant weight was measured using a digital scale. Length and weight were measured at birth, during visits at 1–2 months, 3, 6, 9, 12, 15, 21 and 24 months of age. For the purposes of our study, growth outcomes were assessed at birth, 12 and 24 months of age.Details of outcome assessment have been elaborated on elsewhere. All outcome variables were modelled continuously. We also examined three birth outcomes, namely LBW, classified as birth weight < 2500 g, and SGA, defined as birth weight below the 10th percentile of gestational age- and sex-matched healthy reference population, as dichotomous outcomes. Preterm birth (PTB) was defined as gestational age at birth less than 37 weeks.Two independent personnel measured each child, and repeated measurements were taken. Measurements that differed between the two personnel by 7 mm for length or 50 g for weight were taken again. Means of the final pairs were used in further analysis. Inter-rater reliability was high. Length, weight and weight-for-length, BMI and head circumference were converted to age standardised z-scores using INTERGROWTH-21st standards for newborn size, postnatal growth standards for preterm infants to 64 weeks of postmenstrual age  or WHO child growth standards, as appropriateCovariates adjusted for in models included infant characteristics, such as sex, gestational age at birth and season of birth, and maternal characteristics including age, education, height, BMI, gravidity, vitamin D treatment group, daily protein intake (kg), urinary cotinine levels, maternal smoking and tobacco use during pregnancy, C-reactive protein concentrations at delivery and household asset index.. An asset index was derived using principal component analysis on baseline household characteristic data collected on ownership of various assets, where each participant was assigned an asset score . The asset index was categorised into quintiles.Gestational age was estimated at the time of enrolment using a combination of the last menstrual period and ultrasound. Smoking status was described using urinary cotinine levels, where women with cotinine ≤ 50 ng/ml were classified as non-smokers and women with levels > 50 ng/ml were classified as smokersP-value < 0·05 was considered statistically significant. Descriptive statistics were generated for all outcome variables (growth indices) and Se biomarkers as means and standard deviations, median (inter-quartile range) depending on the shape of variable distributions. Bivariate correlations between all Se biomarkers were evaluated using Spearman correlation coefficients.All analyses were conducted using SAS 9.4 (SAS Institute). A Se biomarkers in maternal delivery or VC specimens for which a growth measure was also available, as presented in We assessed normality of all variables in this analysis using histograms and kernel density plots in order to determine their distribution. Outliers were flagged and examined to determine their biological plausibility, using box plots. Data for this secondary analysis were restricted to those participants with any one of the Se and unit of 1000 for SEPP1. Sensitivity analyses were conducted after including urinary cotinine as a covariate in adjusted models.We used linear regression and generated bivariate and multivariable models adjusting for covariates after generating directed acyclic graphs to account for hypothesised confounding and biological plausibility of associations. Biomarkers were scaled by a unit of 10 for whole blood and serum 1 and 2). Multicollinearity between predictors and covariates in models was assessed using variance inflation factors, and tolerance and collinearity using ‘proc reg’.We also examined associations between selenoproteins glutathione peroxidase and thioredoxin reductase measured in maternal plasma at mid-gestation (17–24 weeks) and delivery and growth outcomes using linear regression, associations with birth weight, specifically (presented in online Supplementary Tables n (%) of children who were SGA, LBW and PTB in this sample were also examined. We conducted additional analyses to examine associations between SGA, LBW and PTB as dichotomous outcomes using modified Poisson regression with robust standard errors to estimate risk ratios for associations between birth outcomes and Se biomarker concentrations in unadjusted and adjusted models.Descriptive statistics for Se and SEPP1 and weight at birth (birth weight and weight-for-age z-scores (WAZ)) and 1 year of age. We hypothesised that SEPP1 may mediate the association between WBSe in VC blood and WAZ/birth weight. We modelled both endogenous (outcome) and exogenous (predictor) variables continuously in structural equation modelling path analysis. Mediation path analyses were conducted using ‘proc calis’ in SAS 9.4 and verified in RStudio using the ‘sem’ function. We examined direct, indirect and total effects. Model fit was assessed using fit statistics including standardized root mean square residual (SRMR) (< 0·08), root mean square error of approximation (RMSEA) (< 0·08), χ2 , comparative fit index (CFI) (≥ 0·90), goodness of fit index (GFI) (≥ 0·95) and Tucker-Lewis index (TLI) (≥ 0·95) and benchmarked based on established criterion. We did not adjust for covariates in path analyses, and results are presented as standardised estimates.In addition to linear models for growth outcomes, we conducted mediation analyses using observed variables to explore potential causal pathways for associations between cord WBWe applied a gate-keeper approach to assess longitudinal associations between growth outcomes and Se biomarkers based on significant associations observed in cross-sectional linear analyses at ages 0, 1 and 2 years. We used unadjusted multilevel models of change (‘proc mixed’) to assess whether relevant Se biomarkers in VC blood predicted a change in growth-z-scores between 0 and 3 years based on the availability of anthropometric data. We also used generalised additive models (‘proc gam’) to examine smoothing splines for predicted associations between Se biomarkers and relevant measures of growth.Se biomarkers, our sample sizes ranged between 435 and 780 for these analyses across growth outcomes. On average, mothers were 23 years of age (sd 4), a majority were educated at a secondary school level or higher, median gestational age at birth was 39 weeks (inter-quartile range 2) and mean birth weight across our sample was 2724 (sd 354) g, with close to 46 % of children categorised as SGA, approximately 25 % were LBW (< 2500 g) and 8 % were born before 37 weeks of gestation (Se at delivery (< 80 µg/l) and 0·2 % of the sample was classified as deficient (< 30 µg/l). Se biomarker concentrations are presented in A detailed description of analytical sample sizes across growth outcomes in our study of mother–infant dyads is presented in estation . A smallρ = −0·00001, P = 0·9; SEPP1 Del and WBSe VC: ρ = 0·03, P = 0·6) in both specimen types.Spearman correlation coefficients for associations between delivery and VC Se biomarkers in our analyses are described in Linear regression analyses are presented for unadjusted and adjusted associations between Se biomarkers and growth outcomes in We examined associations between WBSe and birth weight among infants in our sample. We found negative associations between delivery WBSe and birth weight in unadjusted models, where per scaled unit increased in WBSe, birth weight decreased by 10 g, although results were not statistically significant.Likewise, we found null associations  for LBW per unit (g) increase in maternal delivery WBSe in unadjusted models, with increased risk (12–15 %) after accounting for confounders.In line with our findings for maternal delivery WBSe, we found estimates for associations between VC WBSe and birth weight to be significant with effect estimates suggesting a decrease in birth weight of between 24 and 27 g per unit increase in Se, between unadjusted and adjusted models. Results for risk of LBW were in concordance with our findings for birth weight, with a 6–11 % increased risk of the outcome per unit increase in WBSe in cord blood as presented in 3 and 4). In longitudinal analyses, we found mean LAZ at birth to be −0·12 (SE 0·27), P = 0·27, not significantly different from 0. Average change in LAZ as children age, per unit increase in VC WBSe was −0·004 (SE 0·0017), P = 0·019 (Akaike Information Criterion (AIC): 7392·3, Bayesian Information Criterion (BIC): 7416·2), which suggests that this form of Se has a marginal and non-significant association with linear growth.Associations between LAZ and WBSe in maternal delivery samples were not significant, although we found small negative associations between WBSe in VC blood and LAZ at birth, 12 and 24 months of age. Although effect estimates for associations between WBSe in maternal delivery samples and LAZ were small and in the negative direction, we did not find statistical significance across analyses for WBSe and growth outcomes across age time points. For associations between WBSe in VC blood and LAZ, we found small negative effect estimates across unadjusted models at birth, 1 year and 2 years of age. Although mildly attenuated after adjustment, associations between WBSe in VC blood and LAZ were no longer significant, or in sensitivity analyses, after adjusting for cotinine , although these findings were not significant and confidence intervals for effect estimates were wide.SEPP1, unlike serum and WBSe, showed positive associations with infant birth weight in unadjusted and adjusted models, although results for statistical significance were not consistent across models. Based on our findings, a per unit increase in VC blood SEPP1 was associated with a large increase in birth weight, with estimates ranging between 43 and 82 g between unadjusted and adjusted models. Risk for LBW in our analyses was marginal, with WBSe in VC blood suggesting a protective effect per unit increase in concentrations, although results were non-significant.We did not see significant or consistent associations between LAZ at any age time point and SEPP1 in maternal delivery plasma samples in unadjusted models. We did observe small positive increases in LAZ scores in adjusted models at birth when examining SEPP1 concentrations in VC blood, and associations were significant after accounting for covariates in adjusted models. Effect estimates suggest a stronger association between VC SEPP1 and LAZ at birth up to 2 years of age. These associations, although similar in magnitude, were not significant at 12 and 24 months of age.P < 0·001. Average change in WAZ as children age, per unit increase in VC SEPP1 was 0·0001 (SE 0·0001), P < 0·05 . These findings suggest a marginal protective effect of this form of Se on WAZ.Non-significant positive associations were observed between WAZ and SEPP1 in maternal delivery samples at birth. Significant associations were observed between SEPP1 in VC blood and WAZ. We used uncontrolled longitudinal hierarchical models and found a mean WAZ at birth to be −1·1 (SE 0·1), Weight-for-length and head circumference for age z-score were not associated with SEPP1 in maternal delivery and/or VC blood. We did note that the overall risk for SGA and LBW was marginally lower per unit increase in SEPP1 in both maternal delivery and VC blood; however, these relationships were not significant. Across the different biomarkers, we did note shifts in the direction of trends across the different age points at which growth outcomes were measured.Results from mediation path analysis are presented in Se biomarkers in maternal delivery specimens and VC blood. Figures are presented in online Supplementary Figures 1 and 2. We found consistent inverse U-shaped associations between LAZ, WAZ and SEPP1 in VC blood and similarly between growth z-scores and serum Se in delivery specimens.To examine dose–response relationships between LAZ and weight-for-age, we performed GAM analysis with 3.In this study of mother–infant dyads, we found measures of Se status in maternal delivery and VC blood serum, whole blood and plasma SEPP1 to be modestly associated with infant growth outcomes at birth, 12 months and 24 months of age, with variability in the strength and magnitude of associations across biomarkers and age points. Effect sizes in path analyses were negligible and do not suggest any mediation of the association between WBSe and WAZ at birth or 12 months, by VC SEPP1, likely because WBSe and SEPP1 have differing functions and therefore different impacts on weight and act as part of different metabolic pools that do not interact or share common pathways, as described in online Supplementary Fig. ,19,31–40. A comprehensive comparative list of epidemiological studies is presented in Several studies have examined the effects of Se in a variety of biological specimen types and their associations with infant growth outcomesSe progressively accumulates in fetal organs. Se is stored primarily in the liver of the growing fetus and is likely redistributed after birth, where concentrations in utero remain constant during gestation and decrease in line with stable Se concentration in other organs, during the months following birth. Transfer of SEPP1 from maternal blood to fetus is facilitated by Apo-ER2 mediated endocytosis. Selenomethionine containing proteins and SeMet also supply Se to the fetus,43.During pregnancy, Se and birth weight; r 0·08, 95 % CI 0·01, 0·16 and maternal blood Se and birth weight; r 0·02  on birth weight). In our study, we found a strong negative association between WBSe in VC blood and birth weight ; however, the association between SEPP1 in VC and birth weight ran in the opposite direction . Thus, findings negate our hypothesis that SEPP1 may mediate the association between VC WB Se and weight-related outcomes .In a recent review of studies conducted across a variety of different geographies, results of the association between Se and birth and growth outcomes have been mixed, although overall associations suggested a positive and protective effect of this micronutrient . Non-selenoprotein bound Se concentrations are known to be higher in the placentas of women who experience intra-uterine growth restriction and in mothers of preterm infants. These findings add further credence to our observations around the negative associations between WBSe and birth weight.The negative association between WB. As expected, a plateauing effect was noted in our results, for the association between WBSe and functional selenoprotein, SEPP1 in VC blood at WBSe concentrations of approximately 160 µg/l; however, no distinct plateauing was observed for associations with delivery biomarkers.The protective antioxidant effects of Se bound to selenoproteins including SEPP1 may work to increase birth weight during gestation. This may explain the positive associations with birth weight as observed in our study, given the known antioxidant properties of selenoproteins, which can protect the fetus from free radicals in utero, modulate inflammation and protect biological membranes and DNA during early stages of embryo developmentSe status on placental development and growth-related outcomes, postpartum, may be explained by differences in bioavailability of organic and inorganic forms of the micronutrient. This is important because absorption of these forms of Se, once in the bloodstream, can impact distribution, partitioning and potential toxicity at high concentrations.Mixed findings about the effects of varied biomarkers of . This in turn may impact risk of outcomes such as miscarriage, pre-eclampsia, gestational diabetes and intra-uterine growth restriction.The primary mechanisms whereby Se has been associated with adverse growth outcomes include its essential role in antioxidant defence and its role in mediating oxidative stress, which could impact peri-natal morbidity and mortality. Our results are in contrast to these findings however, where we found higher odds of PTB per unit increase in maternal delivery whole blood and serum Se and WBSe in VC blood. These findings were not significant after accounting for confounding variables. Associations have been noted between lower serum Se and PTB . On the other hand, the risk of PTB was lower per unit increase in SEPP1 in maternal delivery and VC blood specimens, although our results did not approach statistical significance.Low Se status, particularly in women, can impact the risk of PTB. Serum Se concentrations that surpass 80·5–86·9 µg/L can cause an attenuation in the odds of PTB. We noted similar findings in our study, where we saw an attenuation in OR for the highest quintile of serum Se concentrations in our sample  compared with the lowest, and a decreasing trend in OR by increasing quintiles of serum Se.Mechanistically, Se and PTB are linked because of the role this micronutrient plays in the body’s inflammatory response which can in turn cause ruptures to the fetal membraneSe concentrations, particularly during the first trimester of pregnancy. Furthermore, cord blood Se concentrations are known to be significantly lower in premature infants when compared with neonates born at term.Women at increased risk of miscarriage may also have lower serum . We found a per unit increase in concentrations of several Se biomarkers to result in a small and non-statistically significant increase in the risk of SGA. It is likely that inflammation plays a role in our findings, given that median concentrations of C-reactive protein at delivery were 9 mg/l, which are higher than clinically defined thresholds for this acute phase protein (< 5 mg/l). We have therefore adjusted our models to account for potential confounding. We noted an attenuation in the odds of LBW across quintiles of maternal serum Se at delivery, which suggest that higher concentrations of Se are associated with lower odds of LBW , which is consistent with other studies.Similar to other birth-related outcomes, an increased risk for SGA has also been observed in relation to Se, likely driven by mechanisms associated with oxidative stress,39.In our study, we found very small negative associations between WBSe in VC blood and LAZ across age time points, in unadjusted and adjusted linear models, although other Se biomarkers were not associated with LAZ. We observed small effect sizes that were not significant for associations between serum Se at delivery and LAZ. This was in line with the literature for maternal serum Se,53. The syndrome is endemic to regions with low soil Se concentrations. A key feature of the condition is necrosis of chondrocytes in the growth plate of the bone and within the articular surface, which results in growth retardation and osteoarthritis,55. In this condition, Se status may modulate disease susceptibility because of its essential antioxidant activities. Three major environmental hypotheses have been postulated as part of the aetiology of the condition and include soil Se deficiency, contamination of cereals by mycotoxigenic fungi and high humic acid concentrations in the drinking water supply in endemic areas including China and Tibet. In a clinical study conducted in Lhasa, Tibet, where Kashin–Beck disease is endemic and Se deficiency is common, authors found serum Se concentrations to be below detectable levels (< 5 µg/l) in 38 % of the study sample (n 521 subjects). Geometric mean concentrations of serum Se in this study sample for subjects who had Kashin–Beck disease were as low as 10·3 (5·1–20·8) µg/l. These values are significantly below those observed in our study from Bangladesh, where we found mean concentrations of maternal serum Se to be 69 (sd 13) µg/l at delivery. These findings suggest that severe Se deficiency may not be a problem in this Bangladeshi population (83·4 % of our sample was < 80 µg/l for serum Se at delivery and only 0·2 % were Se deficient (< 30 µg/l)).Linear growth has been implicated as a potential outcome of interest in relation to the role of Se in bone growth. Kashin–Beck disease is a chronic osteochondropathy known to result from inherited genetic polymorphisms in Se-related genes which impair collagen synthesisIt is important to note that effect estimates for other growth outcomes in our study were negligible in magnitude and therefore do not suggest that Se biomarkers measured in our study play a major role in birth and growth outcomes in this cohort of mother–infant pairs. We did however find meaningful and substantial effect sizes for the associations between birth weight and biomarkers of Se status. These associations should be investigated further given that different Se biomarkers may act differently on mechanisms of weight gain at birth and in early infancy.Se in a variety of body fluids have been calibrated using various regulatory limits set by the Institute of Medicine (upper limits), USEPA (reference dose) and ATSDR chronic (minimum risk level) and were established using Chinese cohort data to define guideline levels to protect against selenosis. These values range between 400 and 480 µg/l in whole blood and 180 and 230 µg/l in plasma. In our sample, we found maximum levels of WBSe to range between 190·6 and 233·4 µg/l (∼50 % less than WB ranges) in delivery and VC blood and 110·3 µg/l (∼ 60 % less than WB ranges) in serum specimens, which do not suggest risk for toxicity due to selenosis in this population.Biomonitoring equivalents for toxic concentrations of ,58. Se deficiency may contribute to inflammation and pregnancy-related complications, via pathways associated with oxidative stress and may also be associated with growth retardation. At high concentrations, Se can become a pro-oxidant and cause cellular damage due to oxidative stress. In conclusion, we have found that Se may play an important role in placental health and the growth and development of infants and young children in the peri-natal and postpartum period, up to 2 years of age. Future studies should examine, in more detail, the role of Se in linear growth over the infant and young child life course, particularly in relation to its important known functions in placental preservation and birth weight.Evidence exists to suggest that Se has a U-shaped dose–response toxicity curve, with negative health impacts experienced due to deficiency and excess as is evidenced in our dose–response analyses as well


Adolescents who are pregnant and identify as Black are exposed to more societal harms that increase their and their offspring's risk for poor health outcomes. The Colorado Adolescent Maternity Program (CAMP) offers comprehensive, multidisciplinary , trauma-informed obstetric care to pregnant adolescents to ensure the healthiest pregnancy and birth possible and pursue health equity. The present study aimed to examine ethnic and racial disparities in preterm birth and low birth weight before and after implementation of a trauma-informed model of care.Participants were 847 pregnant adolescents  who received prenatal treatment-as-usual (TAU) or trauma-informed treatment. Demographic information, mental health symptoms, and birth outcomes were abstracted from medical records.Overall, findings provided support that implementation of a trauma-informed model of prenatal care led to equitable birth outcomes across racial and ethnic groups. Specifically, Black adolescents in the TAU group were more than twice as likely to deliver preterm or low birth weight infants compared with white and Hispanic adolescents. In the trauma-informed group, however, there were no statistical differences in birth outcomes across racial/ethnic groups, indicating an elimination of disparities in both preterm birth and low birth weight in this population. These more equitable birth outcomes occurred even in the context of adolescents of color having reported more severe depression symptoms postimplementation.These findings provide evidence that a health system-level intervention, herein trauma-informed obstetric care for adolescents, can play a meaningful role in the reduction of racial disparities in birth outcomes. Approximately 1 in 10 infants in the United States is born preterm (<37 weeks of pregnancy), and about 1 in 12 is born with low birth weight (<2500 g).22 In addition, the aforementioned developmental and health consequences of preterm birth and low birth weight further escalate economic ramifications over the life course.24 Targeted efforts to reduce rates of these birth outcomes will, therefore, have wide-ranging benefits for individuals, families, communities, and society.In the United States, annual costs of preterm birth and low birth weight neonatal care are estimated around $5.8 billion—accounting for almost half of all expenditures for infant hospitalizations.25 In addition, infants born to young mothers (younger than 20 years) are more likely to be preterm or of low birth weight.27 Intersectional examinations have also revealed that, among adolescent mothers, Black teens have increased odds of preterm birth and low birth weight.28 A wide variety of mechanisms underlying these disparities have been examined; converging evidence has highlighted the primary role of racism as a social determinant of these birth outcome inequities.29Sociodemographic disparities in preterm birth and low birth weight are well documented. For decades, rates of preterm birth and low birth weight among Black women have been two to three times higher than among white women.31 is an insidious stressor that inflicts harm across the life span on a variety of ecological levels, ranging from interpersonal interactions to institutional policies and cultural norms.32 The role of institutional racism in health care is long-standing and well established.33 Historically, the medical field committed many atrocities against Black Americans and, still today, racism in medicine is evident through entrenched health disparities and differential rates of access to health care. Relevant to maternal–child health, Black pregnant individuals are three to four times more likely to experience a complication or death related to childbirth, and Black infants are more than twice as likely as white infants to die in the first year of life.35Racism, defined as a ranking of people into social groups called “races,” which are used to devalue, disempower, and differentially allocate valued societal resources and opportunities to groups defined as inferior,36 In addition, maternal experiences of racial discrimination have been negatively associated with birth weight and gestational length across numerous studies.37 Together, the racist legacy of medicine and persistent health disparities underscore the need for systems-level change to achieve equitable outcomes and uphold the ethical principles of our profession.Notably, when Black newborns are cared for by Black physicians, this “mortality penalty” is halved.38 starting prenatally. For example, higher frequency of discrimination, as well as a number of contexts in which one has experienced racial discrimination, is associated with increased risk for depression among pregnant women of color.40 This mental health impact of racism further exacerbates risk, as depression also increases the likelihood of adverse birth outcomes.41 Thus, pregnancy represents a sensitive period of development during which a behavioral intervention targeting mental health and adversity, including racial trauma, may confer benefits to both mother and child.Navigating the world as a person of color and being chronically exposed to race-related stress and trauma gets “under the skin” and impacts long-term physical and mental health,The Colorado Adolescent Maternity Program (CAMP) is an obstetric clinic for pregnant adolescents and young women younger than 22. It is a cooperative endeavor between the Departments of Obstetrics and Gynecology and Pediatrics at a large public medical school in the western United States. Patients are either self-referred or referred from community health providers. Given the specialized focus on pregnant adolescents that is not typically found within general obstetrics, community providers often refer adolescents with psychosocial complexity  to the clinic. In 2010, CAMP developed a partnership with the medical center's department of psychiatry to address the mental health needs that were identified within the patient population of adolescents who are pregnant. As a result, a trauma-informed, multidisciplinary behavioral health program was established and included positions for psychology and psychiatry providers as well as licensed clinical social workers.42Social workers meet regularly with patients at obstetric visits to build rapport, assess resource needs, and offer psychosocial support. Patients who are identified as having psychiatric concerns are referred to the HEART  program, which includes psychologists who provide diagnostic interviews and psychotherapy and a psychiatrist who provides medication evaluation and management.43 SAMHSA14 defines a trauma-informed approach as follows:realizes the widespread impact of trauma and understands potential paths for recovery; recognizes the signs and symptoms of trauma in clients, families, staff, and others involved with the system; and responds by fully integrating knowledge about trauma into policies, procedures, and practices, and seeks to actively resist re-traumatization (p. 9).A program, organization, or system that is trauma-informed The Substance Abuse and Mental Health Services Administration (SAMHSA) provided specific guidance for the provision of behavioral health care with a trauma-informed lens, which aligns with the approach implemented in CAMP.44SAMHSA's six key principles of a trauma-informed approach were used to guide clinic-wide changes. See Ashby et al. for detailed description of the trauma-informed model adopted by CAMP.45 and have a higher prevalence of abuse history.8 As predominantly adolescents of color, they are exposed to racial trauma in various contexts including health care. Indeed, a previous article documented that more than one-third of CAMP patients disclosed a lifetime history of trauma and abuse.44 These accumulated social adversities directly impact maternal mental health and the developing child, and thus, a prenatal trauma-informed intervention has the potential for intergenerational impact. For example, Ashby et al.44 demonstrated that implementation of the trauma-informed approach described above improved birth weight outcomes as well as prenatal care engagement among CAMP patients.The relevance of a trauma-informed model of care to an adolescent obstetric clinic is underscored by the intersection of identities in the patient population that increases its exposure to adversities and the subsequent experience of mental health difficulties. As adolescent expectant mothers, they often experience social stigmaThe present study builds on these findings through examination of whether the new model of care impacted racial disparities in birth outcomes. Such an examination highlights the potential impact of trauma-informed care on populations of pregnant adolescents historically impacted by low birth weight and preterm birth.CAMP provides an ideal framework for studying the impact of a trauma-informed program on racial disparities in birth outcomes among pregnant adolescents. Collection of data from patients preimplementation and postimplementation of the trauma-informed approach to obstetric care affords the comparison of birth outcomes between the two models: prenatal treatment-as-usual (TAU) and trauma informed. Our primary objective was to compare racial disparities in preterm and low birth weight births in the TAU and trauma-informed groups. A secondary objective was to examine mental health symptoms at the time of prenatal care initiation across ethnic/racial groups, to provide some psychosocial context regarding the risk of adverse birth outcomes.M=18.3 years, range=12–22 years of age) who received obstetric care through CAMP in 2007–2008 (TAU) or 2012–2013 (trauma-informed), and their babies. Of the total sample, 41% identified as Hispanic, 32% Black, 21% non-Hispanic white, and 6% were another racial/ethnic group . See Participants were 847 young women  in the patient population, the categories used in the current sample were Hispanic, non-Hispanic Black, and non-Hispanic white.Patients provided self-report of their race,46 birth weight was recorded in grams, with low birth weight defined as under 2500 g. Gestational age was recorded in weeks, with preterm birth defined as under 37 weeks of gestation.Consistent with the CDC guidelines,50 a well-validated and widely used 20-item measure of depression symptoms . In analyses, we used the established clinical cutoff score of 16 to identify patients with positive depression screeners.50Depression symptoms were measured with the Center for Epidemiologic Studies-Depression scale (CES-D),Chi-square tests were used (1) to compare racial/ethnic disparities in rates of low birth weight in the TAU and trauma-informed groups and (2) to characterize mental health symptoms of CAMP's patient population at initiation of prenatal care in both groups (TAU and trauma-informed). Analyses were conducted using SPSS, Version 28. Deidentified data and SPSS syntax are available upon reasonable request.p=0.011) and low birth weight  compared with all other racial/ethnic groups. In the trauma-informed group, however, Black patients did not significantly differ in either their rates of preterm birth  or low birth weight  from patients of other racial groups . Further examination of the trauma-informed group revealed that Black adolescents (57.5%) were more likely to have positive depression screeners than non-Black adolescents , and white adolescents (36.0%) were less likely to have positive depression screeners than non-white adolescents . Thus, Black CAMP patients in the trauma-informed group were psychosocially more at risk for adverse birth outcomes. See Patients in the trauma-informed group (48.3%) were significantly more likely to have positive depression screeners than patients in the TAU group  or trauma-informed prenatal care in the Colorado Adolescent Maternity Program (CAMP). In the TAU group, established racial disparities in rates of preterm birth and low birth weight in the United States were replicated, such that Black adolescents were more than twice as likely to have a preterm or low birth weight baby compared with adolescents of other racial/ethnic groups.Pregnant adolescents who identify as Black are more likely to deliver an infant preterm or with low birth weight compared with other racial and ethnic groups.were not more likely to have babies with adverse birth outcomes  compared with adolescents of other racial/ethnic groups. Together, these findings demonstrate that implementation of a health care system-level trauma-informed approach may play a critical role in achieving health equity in adolescent prenatal care. Of note, the observed reduction of racial disparities in the current sample occurred in the context of the Black patient population in the trauma-informed group endorsing higher rates of depression, an established individual-level risk factor for adverse birth outcomes.41 This finding suggests that trauma-informed care may serve as a buffer between maternal distress during pregnancy and birth outcomes.In the trauma-informed group, however, Black adolescents 51; thus, services focused on this developmental period are effective, efficient, and preventative in nature. That the trauma-informed sample had improved racial equity in birth outcomes has notable implications for long-term child and family wellness, as the well-being of mothers and babies is intrinsically interconnected.52 Preterm birth is a leading cause of neonatal morbidity and mortality,53 and preterm birth and low birth weight increase risk for a wide range of medical complications across the life span.20 In addition, having a preterm infant has been linked with poorer family functioning, such as increased debt, financial worry, and parent social isolation.54 These burdens are further amplified for families of color.55The prenatal period is a particularly sensitive one for not only the child but also the motherConsidering the larger context of CAMP patients' lives, significant improvements in birth outcomes for Black adolescent mothers likely compound enduring benefits in terms of child health and development and holistic family functioning. Thus, the current findings provide evidence that modifiable health system practices can have a powerful impact on broadly improving the health of communities of color. Such efforts are long overdue.56 These racial disparities and efforts to dismantle them deserve additional empirical attention.The current findings should be interpreted in the context of study limitations. Primarily, while the programmatic change in CAMP's model of care afforded examination of birth outcomes before and after integration of a trauma-informed approach, the data cannot speak directly to causing improved birth outcomes. A randomized controlled trial of trauma-informed services within obstetric care would provide needed causal evidence for the effects observed in the present study. Furthermore, our sample lacked adequate representation of additional ethnic/racial groups that have been historically impacted by high rates of preterm birth and low birth weight, such as individuals who identify as Pacific Islander or Native American.In addition to the future directions suggested to address limitations of the current study, future research to examine possible mechanisms of change underlying the implementation of trauma-informed care and subsequent improvements in birth outcomes is needed. Mixed-methods approaches utilizing qualitative and quantitative data may be especially informative. For example, interviews with patients and medical providers regarding the trauma-informed approach may identify key mechanisms, such as reductions of racism in the health care system, increased attention to social determinants of health, and increased comfort around addressing mental health concerns. Identification of such mechanisms would support replication of a trauma-informed adolescent model of prenatal care in other health care settings.To further understand the long-term impacts of a trauma-informed adolescent prenatal clinic and provide additional rationale for policymakers to advocate for such programs, follow-up investigations of the patients and their infants would be valuable. We encourage future studies to examine adherence to well-child health care visits, offspring developmental and health outcomes, and parent–child relationship quality, as the benefits of a trauma-informed approach likely extend far beyond birth outcomes.


Empagliflozin did not significantly affect the baroreflex neural or peripheral arc, despite significantly increasing urine glucose excretion  in the 7th and 8th sequences. The possible sympathoinhibitory effect of empagliflozin may be an indirect effect associated with chronic improvements in renal energy status and general disease conditions.Although suppression of sympathetic activity is suggested as one of the underlying mechanisms for the cardioprotective effects afforded by sodium–glucose cotransporter 2 (SGLT2) inhibitors, whether the modulation of glucose handling acutely affects sympathetic regulation of arterial pressure remains to be elucidated. In Goto–Kakizaki diabetic rats, we estimated the open-loop static characteristics of the carotid sinus baroreflex together with urine glucose excretion using repeated 11-min step input sequences. After the completion of the 2nd sequence, an SGLT2 inhibitor empagliflozin (10 mg kg Empagliflozin increases urine glucose excretion by inhibiting sodium–glucose cotransporter 2 (SGLT2) at renal proximal tubules. Although empagliflozin was developed to treat diabetic mellitus (DM), the EMPA-REG OUTCOME trial revealed that empagliflozin can exert a beneficial effect on cardiovascular diseases . The car+/K+ ATPase activity. The ATP level in the proximal tubules decreases within 2 min after renal ischemia , 1817, 1b0 and b1 denote the intercept and slope, respectively.The static characteristics of the baroreflex peripheral arc were quantified using linear regression Eq.  18],2\d,2\d18],2The baroreflex equilibrium diagram combines the neural and peripheral arcs on a pressure versus SNA plane , 20. The−1) during each step was calculated from an increment of UV summed from bilateral ureters. The normalized UF  was defined as the UF divided by the body weight of the rat.The urine flow  for a single kidney was calculated using nUF, the urine creatinine concentration obtained in each of BL, T1, T2, and T3 periods, and the plasma creatinine concentration measured at the end of the experiment, on the assumption that the plasma creatinine concentration had not changed significantly during the experiment. The nUF value corresponding to the AP at the operating point was estimated on the AP–nUF relationship and used to estimate Ccr.Creatinine clearance .cr, nUF-intercept, and nUF-slope were analyzed using repeated-measures one-way analysis of variance (ANOVA) with the Greenhouse–Geisser correction, followed by a Dunnett's test . For the parameters of the baroreflex function, the comparison was made between BL and T3 periods using paired t-tests because the volume loading effect from a drug administration nearly diminished during T3 in the vehicle group. In all the statistical analyses, the differences were considered significant at P < 0.05.All data are expressed as mean ± SE values. The plasma glucose and creatinine concentrations were compared between the vehicle and empagliflozin groups using unpaired t-tests . The tim−1, P = 0.513).The blood glucose levels measured by a tail artery puncture at the beginning of the experiment were not significantly different between the vehicle and empagliflozin groups .The vehicle solution significantly increased the averaged nUF during T1 and T2 Fig. a, but th−1, P = 0.854). Although the vehicle solution reduced the urine creatinine concentration during T1 compared with BL, the effect was not significant during T2 or T3  immediately suppressed SNA . Considering that the molecular weight of empagliflozin (450.91) is only twice as large as clonidine hydrochloride (266.55), clonidine revealed a central sympathoinhibitory effect at a concentration far below that of empagliflozin. Although the strain difference existed [GK in the present study versus Wistar–Kyoto (WKY) rats in our previous study], the acute sympathoinhibitory effect of empagliflozin was minimum, if any, compared with clonidine.The neural effect of empagliflozin contrasts with that of clonidine, a central antihypertensive, examined in our previous study using the baroreceptor isolation procedure . In thatA previous study demonstrated that a two-week treatment with dapagliflozin decreased the norepinephrine content in the kidneys in high-fat fed mice . Gueguen−1·h−1 during T3, which exceeded the fluid infusion rate of 6 mL·kg−1·h−1 (4 mL·h−1·kg−1 of Ringer’s lactate solution plus 2 mL·h−1·kg−1 of anesthetics). Although the negative fluid balance should have reduced intravascular volume, the peripheral arc did not change significantly  decreased the plasma glucose concentration with a nadir at approximately 1 h [Empagliflozin increased the urine output and urine glucose excretion from T1, and the increasing effects continued until T3  is not significantly different from Ccr of the intact kidney in WKY rats  [cr of GK rats is not different from Ccr of Wistar rats at 2 months of age, and significantly decreases at 8 and 14 months of age [Empagliflozin significantly increased Cect Fig. d. Howeveoup Fig. c makes ttty rats . Ccr dur t-test)  estimates of age . The GK Under baroreflex open-loop conditions, baroreflex-mediated changes in SNA yield a positive relationship between SNA and AP in the peripheral arc Figs. e, 2e. An−1·kg−1·mmHg−1, n = 7) is significantly lower than nUF-slope of the intact kidney in WKY rats  [cr is relatively maintained (see the previous section). A histological analysis on GK rat kidneys indicates that diffuse thickening of glomerular basement membrane occurs from 12 weeks of age and becomes more prominent at 16 to 24 weeks of age [In the present study, nUF-slope was near zero in two rats in the vehicle group Fig. a and neg t-test) . Hence, s of age . Such a As we only examined the acute effects of empagliflozin under anesthetized conditions, the results may not be directly applicable to understand any chronic effect of empagliflozin. One difficulty in examining the chronic effect of a test drug on the sympathetic regulation is that the level of SNA is difficult to compare between different time points or between different groups because the absolute amplitude of SNA can be affected by recording conditions. When SNA is expressed in normalized units, a potential difference in SNA could be obscured. One way to circumvent the problem is to calibrate SNA against plasma noradrenaline concentrations . HoweverThe sympathetic suppression via the SGLT2 inhibition was not detected within the observation period despite the significant increase in urine glucose excretion and the reduction of plasma glucose concentration in the present experimental settings. It would take some time for the manifestation of possible sympathetic suppression after the SGLT2 inhibition, and the sympathoinhibitory effect may be an indirect effect associated with chronic improvements of renal energy status and general disease conditions.


A 61-year-old man developed severe swelling in the left lower extremity after interventional embolization of liver tumor. Ultrasound examination showed a pseudoaneurysm and thrombosis in the upper thigh on the left. To recognize the causes and determine the effective therapy, lower extremity arteriography was performed. The results revealed a pseudoaneurysm arised from deep femoral artery. Considering of the size of cavity and symptoms of patient, a new method was tried instead of traditional treatment using PROGLIDE device. Postoperative angiography showed a powerful blocking effect. This case study provide us a specific treatment for pseudoaneurysm, and this method provide us a new therapeutic strategy in clinical practice. In clin2.via another 6-F sheath over right femoral artery access. The catcher is used to catch the guide wire from the contralateral sheath (A 61-year-old male suffered pain and swelling in her left lower extremity after a interventional operation. He had a medical history of interventional embolization of liver tumors 1 month ago. Vascular ultrasound clearly revealed a pseudoaneurysm connecting with left deep femoral artery with a symbol of mural thrombus within the lumen. Surgery was arranged on the 5nd day. Routine preoperative examination was evaluated prior to the surgery. Angiography result revealed a 2 cm × 5 cm-sized pseudoaneurysm arising from a branch of the left deep femoral artery . After tl sheath . A PROGLl sheath , and thel sheath . The vit3.Iatrogenic pseudoaneurysm is a vascular complication after interventional examination. In clinical practice, color doppler ultrasound was used to observe characteristic reciprocating signal of blood flow in the aneurysm cavity . ConsideWe reviewed the relevant literature to find the solution of pseudoaneurysm, the method varies based on size of cavity and symptoms of patients. A cavity <2 cm in diameter that is not extending can be managed conservatively. During conservative procedure, external compression of the puncture can be the first option . If failOur study demonstrate another important function of PROGLIDE closure device, an excellent blocking effect depend on the combination of the closure device and guide wire was observed. This report describes a specific treatment of pseudoaneurysm, and this method would provide us a new therapeutic strategy in clinical practice.


Neonatal hyperbilirubinemia (NH) is a frequent condition that, if left untreated, can lead to neurological disability and death. We assessed the prevalence of NH and associated neonatal and maternal risk factors in 362 mothers and 365 newborns in a semi-rural area of the Democratic Republic of Congo. In addition, we explored the knowledge and practices of mothers regarding this condition. We collected demographic data, anthropometric data, and obstetric and medical anamneses. We examined newborns at birth and at 24, 48, and 72 hours and measured bilirubin at birth in umbilical cord and capillary blood and thereafter in capillary blood. Hemoglobin, hematocrit, ABO group, Rhesus factor, glucose-6-phosphate dehydrogenase (G6PD) deficiency, Hemoglobin S (HbS), and malaria were assessed in mothers and newborns. Among 296 newborns , 5.7% developed NH (95% CI: 3.4–9.0) between 24 and 72 hours according to National Institute for Health and Care Excellence (NICE) UK guidelines. There was a significantly higher risk in newborns with G6PD deficiency , preterm births , newborns with excessive birth weight loss , and hyperbilirubinemia at birth . Newborns with feto-maternal ABO incompatibility and G6PD deficiency had significantly higher bilirubin at birth than others. More than 60% of mothers had adequate knowledge of NH, but compliance with phototherapy in the absence of symptoms was low. Although risk factors for NH are common in this area, prevalence was not high, suggesting a need for better case definition. Implementation of point-of-care devices for diagnosis and awareness programs on risk prevention could help reduce neonatal morbidity and mortality associated with hyperbilirubinemia in these areas. Neonatal hyperbilirubinemia (NH) is common among healthy newborns and usually resolves spontaneously within a week. The excess of unconjugated bilirubin in plasma is the result of a transient imbalance between bilirubin production, mostly derived from the breakdown of red blood cells, which have a higher concentration and a shorter life span than in adults, and its elimination by the immature liver. Conditions that increase bilirubin production and/or decrease its excretion may exacerbate this imbalance. Unconjugated bilirubin is a neurotoxic lipid-soluble compound that, if in excess, can cross the blood-brain barrier causing acute and chronic encephalopathy and long-term neurological sequelae (kernicterus spectrum disorder) and can lead to neonatal death. Morbidity and mortality are largely preventable if cases are identified and treated early. Where available, effective treatment includes blue-light phototherapy and in severe cases exchange transfusion. Known neonatal and maternal factors associated with an increased risk of NH are preterm birth , low birth weight  or small for gestational age (SGA), maternal-fetal ABO or Rhesus incompatibility, and inherited neonatal disorders such as glucose-6-phosphate dehydrogenase (G6PD) deficiency and Gilbert’s syndrome. Postnatal factors include birth trauma, infections, inadequate breastfeeding and dehydration in the first few days of life, and exclusive breastfeeding (late-onset hyperbilirubinemia). Pregnancy-associated complications and intercurrent diseases that increase the risk of intrauterine growth restriction (IUGR), preterm birth, or LBW/SGA can increase the risk of NH.It is estimated that worldwide this condition affects at least 481,000 term or near-term newborns annually, causing 114,000 deaths and more than 63,000 cases of moderate or severe disability.–,,–The Democratic Republic of Congo (DRC) has one of the highest neonatal mortality rates in the world: 27 per 1,000 live births.This prospective observational study was conducted at the antenatal care (ANC) center and maternity ward of Maluku Referral Hospital, Kinshasa, DRC. The hospital is located in a semi-rural area and serves an estimated population of ∼200,000 people. Women were invited to participate when they attended their last ANC visit or on the day of expected delivery and were enrolled on the day of delivery. We included mothers of any age who consented to participate and to stay 72 hours in the hospital after giving birth. We excluded newborns whose health conditions in the judgment of the clinician made it difficult to comply with study procedures. Participants were invited to come back with their newborn for a follow-up visit at day 7.This study was conducted in agreement with the Declaration of Helsinki ethical principles for medical research involving human subjects. Research ethics approval was given by the research ethics committee of the Kinshasa School of Public Health (ESPI/CE/013/2019) and the University of Oxford . The study was approved by the Ministry of Health of the DRC. All participants agreed in writing before enrollment and after receiving adequate explanation in their preferred language. For women who agreed to participate at the ANC visit, full informed consent was obtained on that day, and a signed confirmation was sought on the day of delivery (two-step informed consent). The aim was to interfere as little as possible with hospital procedures and to avoid further stress to the mother during labor. Women who were invited the day of delivery were consented before childbirth.Demographic and anthropometric data, self-reported obstetrical, medical, and drug history in the month prior to enrollment, were collected. Young maternal age (teenager) was defined as < 19 years old.Newborns were examined immediately after birth. Data on sex, weight, length, head circumference, vital signs, and Apgar scores at 1, 5, and 10 minutes of life were collected. Newborns were evaluated for visible signs of hyperbilirubinemia. A blood sample was taken from umbilical cord blood (UCB) and heel prick (capillary blood). Total serum bilirubin (TSB) and direct bilirubin (DSB) levels were measured at birth from UCB and capillary blood and at 24, 48, and 72 hours or until the start of phototherapy from capillary blood. In a subgroup, total serum bilirubin (TSB) and direct serum bilirubin (DSB) were measured also at day 7. The UCB sample was used to measure Hb and HCT and diagnose malaria and G6PD deficiency. Preterm birth was defined as occurring before 37 weeks, LBW as less than 2,500 g, and SGA and large for gestational age (LGA) as less than the 10th centile and higher than the 90th centile, respectively, using INTERGROWTH-21 standards.Malaria Ag P.f., Abbott, Chicago, IL). Hemoglobin and HCT were measured by HemoCue® 301  and Hawksley Haematospin 1400 , respectively. Anemia in the mother was defined as mild, moderate, or severe using WHO cutoffs.,Bilirubin was measured using a FUJI DRI-CHEM 4000i automated system. Malaria was diagnosed by Rapid Diagnostic Test  and standard microscopy methodology. In a subgroup of newborns, malaria was assessed using ultrasensitive RDTs  in the separate models and were assessed using Akaike’s information criterion and log likelihood. Breastfeeding was not included as a risk factor because all mothers breastfed their babies. All models were adjusted for bilirubin levels at birth. A cutoff for the prediction of NH using UCB was identified using area under the operating characteristic curves and the Youden index. Quantitative and qualitative data were entered using MACRO and analyzed with STATA version 17.0 .The primary outcome was the prevalence of NH at 24, 48, and 72 hours, defined as a TSB level above the threshold for phototherapy according to National Institute for Health and Care Excellence (NICE) nomograms based on EGA at birth.N = 110) came back for a visit after 1 week, and their newborns were visited and tested for bilirubin.Between March 2019 and December 2020, 849 births occurred at Maluku Hospital. In total, 362 mothers with 365 newborns were enrolled . AdherenN = 2; IQR: 1–4). The most frequently reported medical condition was urinary and/or genital tract infection (12.7%). Two women reported having been diagnosed with hypertensive disorder and one with maternal diabetes. Only two women reported having had a previous preterm pregnancy, and four had a previous newborn with clinical jaundice. Most women (94.2%) reported having adhered to the malaria intermittent preventive treatment with sulphadoxine-pyrimethamine . Median EGA at delivery was 39.4 weeks (IQR: 38.0–40.6). Ten women could not recall their LMP date, and 36 provided only the month. This group of women was younger than the entire cohort: median age 22 years (IQR: 19.4–26.1 years) versus 25.9 years (IQR: 20.9–32.7 years); P = 0.003. Mean (SD) Hb was 11.3 (1.5) g/dL, with 37% of women having mild to severe anemia. Sixty-one women (16.9%) were positive for malaria by RDT, and 60 were confirmed by microscopy as having Plasmodium falciparum mono-infection, with a mean parasitemia of 1,341 trophozoites/µL . Malaria occurred more frequently in primigravidae  and in younger women . The allelic frequency of HbS was 10.8% . The prevalence of G6PD deficiency was 1.9% by FST and 2.2% by RDT.Most women (79.8%) agreed to participate on the day of delivery, and 20.2% agreed at their last antenatal appointment. The median age was 25.3 years (IQR: 20.8–32.1), and 13.6% were teenagers. The majority of mothers (72.4%) were multigravidae . The mothers of these five newborns also had malaria. The allelic frequency of G6PD A- (202G>A) was 14.6% in males and 15.5% in females (N = 348), FST detected 26.9% of the hemizygous males (7/26) and 33.3% of the homozygous females (1/3). The prevalence by RDT was 3.1% and, compared with PCR results , detected 25% of the hemizygous males (4/16) and the only homozygous female. Both FST and RDT failed to detect any of the heterozygous females.All 365 births occurred by vaginal delivery. Of these, 11 were twins . Mean (SD) birth weight was 3,121 (456.8) g, and 6.8% were LBW. Fifty-three newborns (14.5%) were preterm, 18.8% SGA, and 12.3% LGA. The mean Apgar scores at 1, 5, and 10 minutes were 8.4, 9.2, and 9.9, respectively; 7.4% had a score < 7 at 1 minute and 1.4% at 5 minutes, and none had a decrease between 5 and 10 minutes. None of the newborns presented with discoloration of the bulbar conjunctiva, skin, palm, or sole. Three newborns had clinically suspected sepsis (0.8%). Forty-six dyads (12.6%) had feto-maternal ABO incompatibility, and six (1.7%) had Rhesus incompatibility (but only four mothers were multigravidae). None of the newborns had polycythemia. All mothers breastfed, with most starting immediately (99.5%). Within the first 72 hours (or until diagnosis of NH), 39 newborns lost ≥ 7% of their birth weight. The UCB was positive for malaria in three newborns by ultra sensitive RDT (usRTD), two by standard RDT, and one by microscopy . Total serum bilirubin was also significantly higher among newborns with ABO incompatibility (P = 0.035 for capillary blood and P = 0.031 for UCB) and in those with G6PD deficiency  or 40 µmol/L (for preterm newborns). These cases were kept under observation, and bilirubin was measured again at scheduled time points, except for one case whose mother self-discharged at 48 hours. Median (IQR) TSB in capillary blood was significantly higher than in cord blood: 34.2 (27.4–39.3) µmol/L versus 27.4 (22.2–35.9) µmol/L; P < 0.01), preterm birth (P = 0.007), excessive loss of birth weight in the first 72 hours (P = 0.025), and suspected neonatal sepsis . There was a borderline association with higher mean Hb levels at birth (P = 0.045) and a lower median EGA at birth (P = 0.046). The only maternal risk factor significantly associated with NH was G6PD deficiency diagnosed by FST . Multivariable analysis identified newborns with G6PD deficiency being 21 times more likely to develop NH compared with wild-type newborns : 21.0; 95% CI: 4.1–105.9; heterozygous females: aOR: 9.1; 95% CI: 1.5–53.5). The odds of NH were also higher among preterm births  and newborns with excessive birth weight loss . The risk of NH increased with increasing levels of bilirubin at birth .The neonatal risk factors associated with NH were G6PD deficiency , a specificity of 36.2% (95% CI: 30.6–42.1%), and an area under the receiver operating characteristic (ROC) curve of 68.1 (95% CI: 65.3–70.9). However, as the maximum calculated Youden index was below 50% (36.2%), this indicates that UCB screening would not be a useful test in the study population. Noting that the positive and negative predictive values  are dependent on prevalence, the PPV was 8.72% (95% CI: 5.16–13.6%) and the NPV was 100% (95% CI: 96.4–100%).Supplemental Table 3). About half (52%) had a secondary or higher level of education, 45% had a primary level education, and 3% had no education. Only 3.7% were employed. Participants belonged to 78 different ethnic groups, reflecting the large ethnic variability of the DRC (> 250 ethnic groups). The most represented (each ≥ 5% of the sample) belonged to the main cultural clusters of the center-south of the country.Most women (98%) agreed to complete the questionnaire . Nurses and community health workers were the most frequently reported source of information (84.5%). Four women (1.1%) reported that they had a previous newborn with jaundice, and none received phototherapy .More than half of the women (65.5%) had heard of jaundice before the survey and were able to recognize a jaundiced newborn when shown a picture (59.6%). Women who were older and/or multiparous and had a higher level of education were significantly more likely to have heard of jaundice and to be able to identify a jaundiced newborn from a picture (Just over 1 in 10 women (11.9%) reported that they knew why a newborn could become jaundiced, and most attributed it to an infection or illness of the newborn and/or of the mother. Regarding symptoms, 59.9% of women felt that they were able to recognize them, and 61.3% correctly identified a yellowish discoloration of the skin and eyes as a sign, which was considered harmful by most women (59.3%). Regarding complications, 69.8% of respondents agreed that if a newborn becomes very jaundiced, he/she might become sick, might refuse to feed (47.1%), might develop convulsions (21.2%), might develop brain damage (29.7%), and might die (61.3%), whereas 22% of respondents did not know of any complications that can result from it. Regarding long-term consequences, 58.5% of respondents agreed that jaundice could result in death, delayed development (30.5%), brain damage (29.1%) and convulsions (21.8%), or deafness (10.5%).The majority (98.6%) of mothers reported that they would bring their newborn to the hospital if they developed the symptoms of jaundice; 6.8% would use an herbal/traditional treatment either orally or by topical application, or would give more milk (1.4%), and 3.1% would expose the newborn to sunlight. A minority (11%) used naphthalene  in the house and for storing newborn’s clothes (5%); 2.3% used menthol or camphor-based ointments on their skin. Most women (96.9%) stated that they would be interested in participating in a focus group to discuss this problem in the community, and 96.6% were happy to be contacted in the future for this purpose (data not shown).,In this cohort of newborns in a semi-rural area of Kinshasa, hyperbilirubinemia occurred in 6% of cases in the first 3 days of life. As observed elsewhere, G6PD-deficient newborns had the highest risk of developing hyperbilirubinemia owing to a mechanism only partially explained by increased hemolysis.,,https://intergrowth21.tghn.org).Preterm newborns were six times more likely to develop NH than term newborns. The cause lies in the reduced efficiency of the immature liver and gastrointestinal system in metabolizing bilirubin.,Also, newborns who lost excessive weight were six times more likely to develop NH. Many factors can contribute to weight loss. It is more often observed among newborns of first-time mothers who might have difficulties in breastfeeding, as insufficient milk/caloric intake and dehydration can increase the enterohepatic circulation of bilirubin.Bilirubin at birth  was also associated with later development of NH. In this cohort, levels at birth were significantly elevated in newborns with ABO incompatibility. When intrauterine hemolysis occurs (hemolytic disease of the fetus and newborn), the excess of bilirubin resulting from RBC breakdown is removed by the placenta, and after birth, this excess—especially in the presence of other risk factors such as preterm birth—can lead to severe hyperbilirubinemia.–An early “risk score” based on laboratory and clinical findings in the first 24 hours would be useful in identifying neonates at risk of developing NH and to guide both clinical management and parental counseling in cases of early discharge or when postnatal care is inadequate.In this cohort of women enrolled at delivery, we were not able to identify significant maternal risk factors for NH. Although maternal malaria is an important risk factor and prevalence in this cohort was high, we were not able to assess how many episodes occurred during pregnancy, which would have affected fetal development. Maternal anemia was also frequent, but was not associated with NH.,–,,The prevalence of NH in this cohort was lower than reported in other African countries with comparable risk factors.The sample size of this study was small and allowed only the identification of risk factors strongly associated with the outcome of interest or highly prevalent in this population. Furthermore, this was a cross-sectional study in which most women were included at the time of delivery, and this did not allow us to collect more accurate maternal information. Data from the ANC service were limited because of the low number of prenatal visits or quality of the available data or because mothers did not attend that specific service.We found that 60% of the participants had an adequate knowledge of jaundice, its symptoms, and short- and long-term consequences, and most of them (98%) would take their newborn to the hospital in the presence of symptoms. However, despite providing extensive medical counseling, only one in three mothers whose newborn was diagnosed with hyperbilirubinemia agreed to transfer them to the ICU for phototherapy in the absence of visible jaundice or other symptoms. Community-based jaundice awareness programs should focus on prevention, especially in areas/communities where early hospital discharge rates are high.,–Risk factors for NH are common in this semi-rural area of the DRC, but the lack of diagnostic tools and early discharge from the hospital after delivery suggest that its burden is underestimated. New POC devices to improve the diagnosis of NH and of risk factors could help reduce neonatal morbidity. At the same time, the use of phototherapy cotsSupplemental materials