Microbiome asked several experts in the field to present their perspectives on neonatal microbiota establishment and maturation, the impact of C-sections, and the potential for early-life microbiome restoration. In an accompanying editorial, we also outline key questions and knowledge gaps around this topic [Neonatal microbiome initialization and maturation have been a major focus of recent microbiome research. Perinatal influence factors, in particular the birth type by vaginal birth or Cesarean section, have been identified as a critical determinant of early-life microbiota composition and development. Different therapeutic approaches have been proposed and tested for neonatal microbiome restoration in C-section infants, which have received widespread scientific, clinical and public attention. To provide an overview and broader context of the current state of the scientific discourse, is topic .After birth more than during any later time in life, the microbiome undergoes dramatic changes with rapidly rising bacterial density, major initial compositional fluctuations, the stepwise emergence of organ- and site-specific communities and a steady increase in bacterial diversity. The observed rapid rise in bacterial density at some anatomical sites is stunning and challenges our textbook knowledge on tissue homeostasis in the presence of microbial immune stimuli . It may The compositional fluctuations during the postnatal period most likely reflect the influence of endogenous or exogenous mechanisms on early bacterial colonizers, so-called pioneer bacteria –6. BesidAnother finding highlights the non-redundant role of the birth process as an early transmission event. In the adult host, different anatomical locations such as skin, gut or oral cavity are colonized by highly organ- and even site-specific communities. However, this anatomical specialization is not detected directly after birth but emerges only with time , 17. ThiThe initially reduced bacterial diversity opens ecological niches both for commensal and pathogenic bacteria and thereby explains the enhanced susceptibility of neonates to infection . Most liThe bacterial composition during early life appears to be of particular importance since specific microbial signals and metabolic factors influence the immune priming in a non-redundant fashion. Immune priming in turn determines the life-long susceptibility to immune-mediated and metabolic diseases –25. AlsoGiven the accessibility and functional importance, it is tempting to manipulate the early microbiota, i.e. by the administration of selected probiotics, prebiotics and postbiotics  in order to improve the health outcome , 27, 28.For more than a century, epidemiological studies demonstrated that maternal lifetime experiences, namely psychosocial stress, malnutrition, and infectious burden, predict poorer long-term outcomes across a variety of domains . OffspriA conceptual framework emerging from these studies suggests that environmental exposure during pregnancy alters maternal microbiota and these communities are subsequently transferred to offspring, influencing susceptibility to disease. One challenge in establishing causality between maternal exposures, microbiota, and offspring phenotype is that these environmental perturbations exert disruptive effects on both mother and developing fetus. In other words, offspring develop in a prenatal environment that is shaped by lifetime exposures to environmental conditions, and at birth, neonates are colonized by microbiota shaped by the same factors. Innovative approaches and methods are now needed to disentangle the complex interactions between lifetime exposures, the disruption of pregnancy, and colonization at birth. One such effort involved exposing fetal mice to prenatal stress, followed by C-section delivery and inoculation with distinct microbial communities . In thesLactobacillus crispatus, Atopobium vaginae, Gardnerella vaginalis– are recovered from the stool of newborns, providing support for neonatal inheritance of maternal vaginal microbiota [G. vaginalis are two common risk factors associated with increased risk for adverse obstetric outcomes [G. vaginalis, alone or in combination, would affect the offspring postnatal response to CST I or CST IV exposure at birth [A central argument in the debate regarding the safety and efficacy of vaginal seeding and fecal microbiota transplantation procedures hinges on whether birth-associated microbial exposure has any lasting health benefits, such that a lack of exposure prevents the initiation of a developmentally-important event , 47, 48.crobiota . These bcrobiota –52. Speccrobiota –56, suggcrobiota . Epidemioutcomes –63. We eat birth . Surprisat birth . If thesWhile this area of research will undoubtedly contribute significant insight into postnatal microbiota transplantation procedures and effects on health, this topic has also garnered a growing fascination in public discourse over the last several years. Reflecting a trickle-down effect on social attitudes, a recent study examining attitudes towards vaginal seeding reported that pregnant individuals viewed these procedures as replicating a natural process and may help reduce maternal shame and guilt about undergoing c-section . This seC-section delivery impairs the intergenerational transfer of the maternal microbiome, altering natural colonization by pioneer communities of different infant epithelia in different body sites. C-section and pre or perinatal antibiotics are associated with increased risk of autoimmune and metabolic diseases in humans and in mice. Thus, as we perform medical practices that have collateral costs, we need to restore and minimize the damage.Nature design for fish, amphibians, reptiles, birds and mammals- entitles the offspring being born through a canal that is i) colonized by microbes and ii) shared with the defecation canal (cloaca) or adjacent to it (vagina). This non-random design favors transmission of maternal gut bacteria which will successfully colonize the offspring’s gut. Thus, it is not surprising that fecal transplant to newborns is effective in colonizing the infant gut .In humans, the vaginal canal in the late third gestational trimester does contain bacteria shared with feces, and furthermore, shared also with oral, nose and skin sites . This exGiven the serious consequences for the baby of impaired microbiota transmission at birth, restoration needs to be implemented with current state of the art, minimizing both infection risks for the baby and the costs of inaction. Why use “the real stuff”, and not wait until we understand better which are the exact bacteria and when to give them? Because of the complexity of biological fluids (we are still performing blood transfusions because we don’t know yet how to reconstitute blood from purified components).I want to share three ideas regarding neonatal microbiota seeding at birth:Recapitulating natural exposures at birth after careful examination of the maternal vaginal health will not put the baby at higher risk of infections than vaginally born infants. In the crucial windows of infancy, correct programming will determine future health, and thus impacts and perturbations cannot be followed by inaction, but by rehabilitation to provide what was missing to restore organisms and ecosystem functions that are crucial for health.The gut microbiota is being increasingly recognized as an important part of human physiology and a significant contributor to health. This is especially true in infants, where the gut microbiota influences the developing immune system and overall physiology. Gut microbiota composition in infancy is associated with a range of health outcomes in later childhood, most prominently weight and immune health –72. FactBifidobacterium and Bacteroides strains, are naturally transferred from the mother’s gut during birth [The case for microbiota restoration is especially clear for infants born by C-section. The important colonisers of infant gut and primary utilisers of breast milk oligosaccharides, ng birth . They arng birth , leadingng birth . Alarminng birth , 89. In ng birth . InfantsBacteroides and other fecal bacteria [Since the maternal gut is the natural source of microbes to the infant gut, maternal fecal microbiota transfer (FMT) is an effective method of microbiota restoration in CS-born neonates . Mimickibacteria , 48. In bacteria . Oral adbacteria . The vagbacteria , 92, likWhile maternal FMT is effective, it is unlikely to be a feasible standard solution for all neonates. Careful screening of the mother is required due to the potential of transmitting pathogens. Indeed, often the most common reason for intrapartum antibiotic treatment is maternal carriage of group B streptococcus, which can cause a dangerous infection in the infant. Infants of these mothers would benefit from microbiota restoration but FMT may not be a safe option. FMT from a universal donor could be a solution, and an intriguing question is whether FMT from a universal donor is as effective as maternal FMT. While there is some evidence to suggest that strains from an infant’s own mother may be particularly compatible with the infant’s gut , some moBifidobacterium longum subsp. infantis, B. breve, and B. bifidum, are likely to be useful. Since many such strains are currently on the market and safe, their use in C-section-born and antibiotic-exposed infants is highly recommendable. Short-term administration of probiotics to C-section-born neonates in the hospital appears promising [Probiotics can be used to restore at least part of the normal infant gut microbiota , 93, 94.romising  and warrThe long-term health benefits of infant microbiota restoration should be investigated especially in different risk groups. Experimental restoration of gut microbiota provides a way to test causality in the link between infant gut microbiota and later health. Such long-term studies will take time, but there is sufficient evidence to adopt microbiota restoration practices before conclusive results on health benefits are available. In addition to microbiota restoration, however, efforts are needed to reduce microbiota disruption by promoting vaginal birth and breastfeeding, and carefully considering the need for routine prophylactic antibiotics during birth.Bacteroides species, Parabacteriodes species, Escherichia coli and Bifidobacteria species that are highly adapted to co-colonize neonates as an ecosystem in symbiotic relationships that have co-evolved over many millennia [Maternal transmission of microbes to their neonates is an unappreciated form of kinship involving microbes from gut, urogenital, oral and skin microbiotas . Common illennia . After cillennia . There iThe key challenge is to determine how these maternally transmitted microbes influence the longer-term growth, development and disease resistance of a baby . Much ofBifidobacterium (phylum Actinobacteria) are highly adapted for maternal transmission and colonization of the neonatal intestine [Bifidobacterium species described, however, B. breve, B. bifidum and B. longum are commonly found in the neonatal gut microbiotas in the UK [B. longum subsp. infantis is not common in neonates born in any of these Western world countries, but is the dominant founder bacterium in neonates from Low- and Middle-Income Countries Bangladesh [B. longum subsp. infantis has been lost from Westernized human populations due to modern lifestyles, such as diets, antibiotics, etc. Bifidobacteria play a pioneering role in nucleating and shaping the gut microbiota assembly by supporting the acquisition and colonisation of new beneficial microbes through cooperation such as cross-feeding human milk oligosaccharides (HMOs) [B. infantis has been shown to harbour highly evolved pathways that metabolise breastmilk, releasing indole-3-lactic acid to shape immune development [Bifidobacteria that have co-evolved to transmit from mother to child that could potentially be exploited therapeutically.As an example of maternally transmitted bacteria, species of ntestine , throughntestine . There an the UK , Sweden,n the UK . Importangladesh , Gambia ngladesh  and Malangladesh . It is ps (HMOs) , or thros (HMOs) . More reelopment . There aWe need to innovate ways to protect and nurture a baby’s microbiota to optimize growth, development and disease resistance. Understanding the ecological processes and mechanisms of maternal transmission and early life microbiota acquisition and assembly holds the key to biological discovery to enable translational sciences. We need to consider alternatives to antibiotics that spare a baby’s microbiota, and also therapies that can recover/restore the microbiota after antibiotic therapy. Microbiota transplantation studies in neonates using undefined maternal microbiomes have been undertaken but longer-term we envision more sophisticated, defined approaches , 91. A d


The type of maternal caregiving impacts children’s growth and can lead to heritable changes in gene expression. When women become mothers, they adopt parents’ behaviours similar to those received in the family of origin. The study investigates if a birth’s social and cultural content can be seen as heredity transmitted from mother to daughter.A retrospective study was conducted on a group of mothers recruited across Italy through the social network Facebook. The study was carried out using a questionnaire administered from July to September 2021. The survey consisted of 21 questions. The analysis was carried out using STATA 14.Our sample consisted of 6051 mothers; the mean age was 37.7 years. Womens born by spontaneous birth has 2.1 times higher risk of having a spontaneous birth for their first child. Those born by operative labour have 2.7 times higher risk of having an operative delivery for their first child. Finally, those born by caesarean section are 2.3 times more likely to have a caesarean section for their first child. On the other hand, those born by preterm labour have 1.8 times higher risk of delivering their first child preterm. Those who were breastfed have 2 times higher risk of breastfeeding their first child. Women who have been told their birth is an extraordinary event are 2 times more likely to consider the birth of their first child as a problematic but still extraordinary event. Those who received a description of childbirth from their mother as a problematic event are twice as likely to consider the birth of their first child as a traumatic event overall.The results show that transmission, written in the psyche, in preverbal and in internalisations derived from the relationship with one’s mother, is true and strongly present. Also, the ways of one’s own birth are so strong as to have repercussions on the daughter’s own and subsequently also on her children.• The unconscious objects, which are projected onto the children, can also take the form of both physical and psychic somatisations, which are repeated cyclically between generations.• The way in which birth is cared for and the quality of care provided at this unique time in a woman’s life will leave an imprint not only on the woman herself, but also on future generations.


Birth weight is considered a crucial indicator of individual and population health, as it determines a newborn’s growth and development. An extensive body of research has explored various determinants of perinatal health, including the impact of living arrangements. This population-based study analyzes the relationship between mothers’ partnership status and household structure and children’s low birth weights. It addresses two basic research objectives: on one hand, how living/not living in a couple affects birth weight; on the other, how partnership status impact on birthweight when mothers live in extended households with other non-nuclear members.A novel database provided by the Spanish Office for National Statistics (INE), which links the 2011 census with births registered from 2011 to 2015  is used. Llogistic regression models are estimated tto obtain adjusted odds ratios (OR) for the relative effects of living arrangements and other covariates such as characteristics of births and mothers’ socioeconomic profiles, on birth weight.Differences in low-birth-weight rates may be attributed to the dissimilar socio-demographic characteristics of the groups of mothers in the different coresidential situations. Although our models revealed that the impact of the covariates on birth weight was similar to that shown by previous studies, this was not the case for the effect of the main explanatory variable. Contrary to expectations, the presence/absence of a male partner in nuclear or in extended households does not reveal significant protection against low birth weight. Children born in households in which the male partner was absent were not more likely to have a low birth weight. On the other hand, analyzing the possible protective effect of extended households, we did not detect significant differences in the likelihood of low birth weight between single mothers without and with non-nuclear coresidents in their households.Our analysis provides novel evidence regarding the effect of partnership status and household type on perinatal health in Spain. First, contrary to what has been observed in previous studies in Spain and elsewhere, our study shows that living without a partner has no effect on low birth weight. Second, we reveal that households including non-nuclear coresidents are associated with low birth weight suggesting that even in a basically familist societal context such as the Spanish one, the extended family does not fully protect against poor perinatal outcomes. Two interesting lines of research have recently connected the birth weights of newborns and the structure of their mothers’ households. First, birth weight is considered a crucial indicator of individual and population health, as it determines the likelihood of a newborn going on to experience satisfactory growth and development , 2. Low Second, the demographic events of recent decades and their structural, cultural, and social consequences have led to new family patterns differentiated in terms of cohabitation, household type, size, and composition –17. In SPrevious studies in various contexts have connected the research on birth weight and household composition by suggesting that household type may be an important factor in children’s birth weight . This reAgainst this background, it is expected that coresidence with a partner will have a positive effect on perinatal health indicators, specifically on birth weight: cohabiting mothers will benefit from the protective effect of partnership and partner support in avoiding poor perinatal health outcomes and will have fewer low-birth-weight babies than non-cohabiting mothers. In addition, some single mothers may join an extended household as a specific strategy to alleviate difficulties during and after pregnancy. It can be assumed that the family solidarity of the extended household will reduce the incidence of low-birth-weight children, particularly among non-partnered mothers. The protection of the extended household for single mothers is even more plausible given the proven negative educational gradient of single motherhood in Spain , 22. If These expectations led us to formulate four hypotheses. H1: Lacking protection and support from a partner, lone mothers who do not live-in nuclear households have higher rates of low-birth-weight children than women living with a partner do. H2: Because of the protection and support deficit resulting from the lack of a partner, even when supported by an extended household, non-partnered mothers living with non-nuclear coresidents have children with higher rates of low birth weight than partnered women living with non-nuclear coresidents. H3: Non-partnered mothers who live with non-nuclear coresidents have lower rates of low birth weight than non-partnered women who do not live-in extended households. H4: Partnered mothers living in extended households have lower rates of low birth weight than partnered women in nuclear households because the protective effects of a partner and extended household are additive.Our data come from a novel database provided by the Spanish National Statistics Office  that links the 2011 census, which contains information on individuals’ personal characteristics such as gender, age, marital status, country of origin, education level, employment status, living conditions, migration status, and type of household, with information about births registered between January 2011 and December 2015 and vital statistics from the Spanish MNP. The whole dataset represents a sample of approximately 10% of the Spanish population. Individual birth data from the years 2011 and 2012 for mothers aged 15 to 49 living in different types of households were used for this population-based study. As information on household structure is available for the year 2011, the observation period is limited to only two years (2011 and 2012) to avoid possible changes over time in household structure undermining the reliability of the measure. Three exclusion criteria were applied to construct the analytical sample. First, multiple births were excluded since it is known that they have a different intrauterine growth pattern from gestational weeks 28–30. Second, observations with missing information in the relevant variables such as birthweight and gestational age were discarded. Third observations with impossible combinations of birthweight and gestational age based on references published elsewhere  were nota) mothers without a partner and without coresidents outside the nucleus; (b) mothers without a partner but with coresidents outside the nucleus; (c) mothers with a partner but without other coresidents outside the nucleus; and (d) mothers with a partner and with coresidents outside the nucleus. Our analysis includes available covariates that are commonly used as controls in regression models for birth weight. The sex of the newborn is included because on average, girls weigh less than boys [Our dependent variable is low birth weight, which is set below 2500 g according to the threshold commonly adopted in the literature [han boys ; birth ohan boys  gestatiohan boys , 32 grouhan boys  were alsa and c households indicate the effect of not having a partner on birth weight among mothers living without non-nuclear coresidents to test H1. Comparing types b and d shows the effect of not having a partner on birth weight among mothers living with non- nuclear coresidents, testing H2. Comparison of types b and a shows the effect on low birth weight of unpartnered women living with non-nuclear household members, testing H3. Finally, by comparing types d and c, we can estimate the effect of coresidence with non-nuclear partners among women with partners and test H4. The empirical analysis proceeds as follows. After determining the basic descriptive results of the studied population and assessing the total effects of living arrangements on low birth weight, we estimated logistic regression models to obtain adjusted odds ratios (OR) for the risk of giving birth to a low-birth-weight baby. The first model uses the entire analytical sample and includes household type as the focal independent variable, in addition to other covariates that need to be controlled to gain precision and avoid potential confounding factors. Four other logistic regression models are estimated that compare, two by two, in the manner described above, the birth weight outcomes of children born to mothers in different living arrangements. These four models allow separate estimations of the effects of a partner and other non-nuclear coresidents on birth weight. In addition to logistic regression models, we post-estimated average marginal effects to circumvent the possibility that the OR analysis reflects unobserved heterogeneity, i.e., the influence of omitted factors impacting on our dependent variable. As indicated by Mood (2010) [Our analytical strategy is based in a four-way comparison. Comparison of the birth weights of children born in type d (2010)  comparinTable Compared to the other categories, mothers residing in typical nuclear households, with a partner and without non-nuclear coresidents, gave birth to proportionally fewer children with a low birth weight (8.5%), followed by mothers without a partner and without non-nuclear coresidents (9.7%). Mothers without a partner who were living with non-nuclear coresidents.had the highest rate of low-birth-weight babies 11.4%), surpassing the rate for mothers with a partner and with non-nuclear coresidents (10.2%). As shown in Table 1.4%, surIn addition, we can see that the youthfulness of young mothers living without a partner and with non-nuclear coresidents was associated with higher rates of firstborn children, premature gestational age, and lower educational attainment, all factors known to be associated with low birth weight. As Table Table Birth weight is determined by multiple factors. Its main determinants may be biological. i.e., related to the sex of the baby, the weight of the mother, parity at birth, the presence of chronic maternal disease, complications during pregnancyand obstetric difficulties, or behavioral, relating to the habits of the mother . MaternaThis study analyzes the associations of partnership status and living arrangements with the birth weight of babies born in Spain between 2011 and 2012. . Data analysis does not reveal that lack of a partner has a substantive impact on low birth weight in nuclear or in extended households. Children born in households in which the male partner was absent were not more likely to have a low birth weight. The unadjusted ORs were small and not statistically significant and do not back our H1 and H2. Adjusted ORs estimated by logistic regression models  partners against low birth weight in the context of the structure of the households in which they and their female mates lived, a factor rarely considered in this type of analysis. In terms of limitations, our data lacked a set of control variables that are important predictors of birth weight, such as maternal chronic conditions, nutritional status, infections, tobacco, alcohol or drug use, and exposure to poor environmental conditions. This limitation arises from the fact that the birth registry does not include potentially relevant data on maternal health behaviors, health system utilization, or health conditions. Data and methodological limitations also prevent exploration of the causal mechanisms influencing the compositional and behavioral disparities between certain categories of mothers. These issues constitute a promising new field for future studies of the impact of living arrangements on perinatal outcomes.Our analyses contribute to discussions on the determinants of low birth weight in many ways. First, our study challenges previous research findings in which the  partner is an important provider of resources and care with proven influence on the perinatal health of the child. Our results indicated that no such relationship exists in the Spanish case, a societal context where the growing prevalence of single-parent households and their social acceptance is no longer an issue. Second, research on the effect of family status on perinatal health has so far focused mainly on the impact of the mother living with or without a partner within a nuclear household on low birth weight; less attention has been paid to the impact of living arrangements beyond the predominant framework of the nuclear family on birth weight. Although numerous studies have argued that in Spain—and more broadly in southern Europe—the family is an important agent of care and protection, relatively little is known about the protective role of extended families on perinatal health. This study has broadened the framework of analysis by considering diverse household compositions. Our results suggest that the starting situation of lone mothers is so precarious that living with the extended family is not sufficient to mitigate poor perinatal health outcomes. This pattern is especially striking in the case of very young single mothers. Although some single mothers may rely on other family members for support, the extended family is not able to counteract the disadvantageous situation that pushed them to seek this support. In these cases, the support of an extended household does not compensate for the deficits caused by the lack of a partner. Of course, that these households may also become stressors due to their scarce resources  cannot be ruled out. Third, a similar pattern can be observed among partnered women, as the protection provided by extended households did not add to that of being in a couple. This finding might also be due to the fact that the initial disadvantage that led the partnered mothers to seek the protection of non-nuclear coresidents is not reduced by the support that they provide.


The project purpose was to describe nursing hours per patient day (NHPPD) within the Veterans Health Administration (VHA) and to evaluate Staffing Methodology in the VHA Community Living Centers (CLCs) by comparing Staffing Methodology targeted NHPPD with actual NHPPD. Data were compiled retrospectively for each CLC unit over a one-year timeframe for calendar year 2019. VHA had 134 CLCs including 390 nursing units. Nursing units without 6 months of actual NHPPD data were excluded from the data set. For descriptive analyses, actual NHPPD were averaged across months for each unit. The percent of target was calculated as this average divided by the NHPPD target times 100. The percentage of months each unit met the targeted NHPPD was calculated. After data exclusions, the final data set included 322 nursing units from 133 CLCs. The mean for actual hours as a percent of target was 121.6%  indicating that the units’ average hours across 2019 were 21.6% significantly higher than target. Also, half of units met their targets 91.7% of months as reflected by the median. The actual NHPPD significantly differed across months (p< 0.001) with the 2019 months of January and October having the highest NHPPD. Similar results were seen for NHPPD as a percent of target. Veteran safety is a VHA priority and appropriate nurse staffing is key to providing care that improves Veteran outcomes and reduces adverse events. Further exploration is needed on how nurse staffing in the CLCs impacts Veteran outcomes, safety, and satisfaction.


Sepsis is one of the most important causes of morbidity and mortality in the neonatal period, especially in preterms. Diagnosis is difficult because of specific signs and symptoms. The diagnostic gold standard is blood culture, but its sensibility is low. Much effort has been made to identify early, sensitive, and specific diagnostic markers; among these markers particular attention was paid to procalcitonin. However, reference ranges of serum procalcitonin (PCT) shortly after birth have not been sufficiently studied in healthy preterms, and literature is still contradictory.The aim of the study is to define PCT age-specific reference ranges in the first 72 h of life in uninfected VLBW preterms.Serum levels of PCT were assessed for each newborn at birth and every 24 h until the 3rd day of life. The eligible patients were classified into two groups according to their sepsis status.Approximately 343 patients were enrolled; 28 were septic and 315 non-septic. In non-septic infants, 1,015 determinations of PCT values were performed. Our data showed a trend in average value of PCT to increase after birth up to a peak between 24 and 48 h of life and, subsequently, to fall. The average peak value was 15.12 ng/ml achieved at nearly 36 h of life.Our study shows a PCT nomogram of healthy preterms, which is different from the one of term newborns. Data agree with what is reported in literature on the reference ranges and trends of PCT in non-septic preterms shortly after birth. Neonatal sepsis is a clinical syndrome characterized by systemic signs and symptoms of infection and by the presence of pathogen agents in blood, which occurs in the first 28 days of life .Neonatal sepsis still represents an important cause of mortality and morbidity among infants, above all in very low birth weight  preterm infants, with an incidence ranging from 1 to 20/1,000 live births .According to time of infection, we can distinguish early onset sepsis (EOS), during the first 72 h of life, and late onset sepsis (LOS) after 72 h from delivery.Neonatal sepsis presents common and unspecific clinical manifestations so that an infant with a suspect for sepsis requires rapid assessment to guarantee rapid therapy. Blood culture remains the gold standard for diagnosis, but data available from two large randomized controlled trials in recent years have shown culture-negative sepsis rates of 56 and 46%, respectively  and CRP are the most commonly used and have been studied in numerous neonates .Procalcitonin usefulness in EOS remains uncertain, despite its wide use in LOS. PCT differs from CRP for a faster kinetic: Its release from tissues increases during infections more rapidly than CRP and can be detected in circulation within 2–4 h, with peak concentrations achieved after 6–8 h and a half-life of 20–24 h .Several studies have reported the usefulness of serum procalcitonin (PCT) as a potential biomarker for bacterial infections in adults and children, and the reference range is less than 0.1 ng/ml, while the cut-off value for the diagnosis of bacterial infections or sepsis has been established at 0.5 ng/ml. During bacterial or fungal infections, the PCT increased up to 2 ng/ml or even 50–100 ng/ml .These values concern children but not newborns during the 1st days of life, when we can find a physiologic peak of PCT in non-infected newborns  , which mThe PCT reference range during the neonatal period varies greatly depending on gestational age and infectious status. Its values in EOS are considerably higher than those of non-infected infants, and many studies report different age-related nomograms for both term infants and preterms –12. AnywIn our study, we investigated the 95% age-specific reference intervals of PCT values in the first 72 h of life in VLBW preterm infants.Our study population consists of 343 preterm newborns enrolled over 4 years (2017–2020) in the Neonatal Intensive Care Unit (NICU) of Santa Chiara University Hospital of Pisa . Inclusion criteria were GA ≤ 32 weeks + 6 days and/or birth weight ≤ 1,500 g. Absolute exclusion criteria were exitus within 48 h of life, asphyxia, outbirth with transfer to our Center after 4 h of life and absence of informed consent.The patients were divided into 2 groups based on the presence or absence of EOS: (1) non-septic and (2) septic. In Group 2 were included infants with:–Certain sepsis: positive blood culture performed at birth and clinical/radiographic signs of infection.–Clinical sepsis: negative blood culture performed at birth but clinical signs of sepsis, obstetric risk factors of infection, positive skin swab culture performed at birth or a positive bronchial aspirate culture if intubated, positive sepsis screening  and/or radiological signs of pneumonia.To all enrolled patients, empirical antibiotic therapy (ampicillin + sulbactam and gentamicin) was administered from birth to 72 h if EOS was excluded or prolonged for 7–14 days in relation to sepsis.Procalcitonin measurements were performed at birth and every 24 ± 4 h until the 3rd day of life. For all patients were recorded gender, GA, BW, weight percentile, 5-min Apgar score, intubation in delivery room. In combination with PCT, it was always measured CRP. In all newborns, we also examined WBC, liver and kidney function, blood and skin swabs culture, and chest X-ray at birth.Procalcitonin serum assays were performed on samples of blood taken with microtubes in K2-EDTA or in lithium-heparin. The PCT blood concentration was measured by the immunometric electrochemiluminescence technique (Elecsys BRAHMS PCT instrument). According to the EP05-A protocol of the Clinical and Laboratory Standards Institute (CLSI), the inter- and intra-assay coefficients of variation (CV) were, respectively, ≤2.1 and 2.4%.t-test for independent samples (two-tailed).In accordance with the literature, we analyzed the natural logarithm of PCT values (lnPCT). To determine the PCT reference range in the 1st 72 h of life in non-septic preterm infants, we built a graph with the 95% CI. To compare means of two independent groups, we used p < 0.05. SPSSv.27 technologies were applied.Significance was defined as Over the study period, we enrolled 364 preterm infants. Among them, 6 died within the 1st 24 h of life and were not included in the study. Of the 358 remaining patients, 15 were excluded due to perinatal asphyxia. The analysis was drawn up on 343 infants, of which 163 were girls and 180 were boys. Of these, 315 were non-septic, and 28 were septic. The two groups resulted statistically homogeneous relatively to GA, BW, and gender.t = –5.138, p < 0.001), with higher values in septic patients. Similar results were obtained for lnPCT values at birth (t0) , at 48 ± 4 h of life (t2)  and at 72 ± 4 h of life (t3) .The comparison of lnPCT values at 24 ± 4 h of life (t1) showed statistically significant differences between the 2 groups  and the geometric mean, with upper and lower limits of the reference range of the non-septic group (dashed curves). All the values of the septic group at peak were higher than the mean of the non-septic group .p = 0.052). For the GA ≥ 30-week group, the peak was 4.81 ng/ml at 29 h. For the GA < 30 weeks group, the peak was 8.86 ng/ml at 32 h. For the BW > 1,000-g group, the peak was 10.34 ng/ml at 31 h. For the BW ≤ 1,000-g group, the peak was 3.20 ng/ml at 36 h. In To assess any differences in the PCT trend, depending on GA and BW, we stratified the non-septic group on two categories of GA (≥30 weeks and <30 weeks) and two categories of BW , and we constructed reference curves for all groups. We also examined whether there were significant differences for the presence of SGA in the four categories. It was found an increased number of SGA in the BW > 1,000-g category at limits of statistical significance , with higher values in the GA < 30 weeks group.We made comparison of lnPCT values at t1 and t2 for categories of GA and BW. The only significant difference was detected between GA categories at t2 .Other studies show differences in PCT concentration according to gestational age , so we dReports on preterm infants suggested that the physiological rise in PCT concentration of preterm infants may be longer and higher than in term infants. In our cohort, the peak value was actually longer but not higher than that reported in literature for term infants , 10, andIn conclusion, we reported reference ranges for serum PCT concentrations in healthy VLBW preterm newborns during the first 3 days after birth, and we developed an age-related nomogram.A major limitation of this study is that we did not investigate how the severity of underlying illnesses might have hampered PCT response nor the possible influence of newborns factors, such as respiratory failure, which, in literature, is reported as the main effect or for the transient elevation in serum PCT levels in 1st days of life . So furtThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Regional Ethics Committee of Tuscany – Pediatric Section. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.MC conceptualized and designed the study. CT drafted the initial manuscript and reviewed and revised the manuscript. MV and ST collected the data. RM carried out the analyses. LF reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.


Simple hepatic cysts are common lesions in adults, but rare in children. Because of their benign nature, simple hepatic cysts may not be detected until they grow too large to be diagnosed and resected in a minimally invasive manner.An 18-month-old girl presented with an enormous cyst occupying the entire abdomen. The beak sign on computed tomography revealed the hepatic origin of the cyst. The cyst was decompressed through the umbilicus, which was opened by the three-triangular-skin-flap technique, thus creating a working space that enabled laparoscopic surgery. The cyst was excised en bloc together with the attached hepatic parenchyma.Giant simple hepatic cysts occupying the entire abdomen are rare in children. Of 14 reported cases, only 1 underwent laparoscopic treatment. We have herein reported another case of a giant simple hepatic cyst in which the beak sign on imaging and the three-triangular-skin-flap umbilical opening technique were useful for its diagnosis and laparoscopic excision, respectively. Complete excision is desirable because there is a possibility of recurrence or other diseases that require total removal, including hydatid cysts and mesenchymal hamartomas. A simple hepatic cyst, also called a solitary nonparasitic cyst of the liver, is a congenital cyst with a fibrous wall lined by a simple cuboidal, columnar, or rarely squamous epithelium –4. Such An 18-month-old girl presented with abdominal distension without abdominal pain. A cystic mass was palpable over the whole abdomen without tenderness. There were no other symptoms caused by the mass effect. Ultrasonography revealed a large unilocular, sonolucent cyst. Abdominal computed tomography (CT) showed that an enormous unilocular cyst occupied the entire abdomen Fig. . In totaWe searched PubMed using the terms “simple hepatic cyst,” “simple liver cyst,” “nonbile containing intrahepatic cyst,” or “solitary nonparasitic cyst” and “pediatric” or “children.” We also searched Ichushi-Web using corresponding Japanese terms. The references of each article were searched for the complete collection. The criterion for enormousness was that the cyst extended into the pelvis and the transverse diameter was more than 75% of the abdominal cavity. The cases collected through this search are summarized in Table Reports describing 14 children aged ≤ 15 years with simple hepatic cysts occupying the entire abdomen were collected (Table Percutaneous aspiration of the cyst results in universal recurrence, but aspiration may be appropriate as a temporary procedure for fetuses or neonates with life-threatening symptoms , 4, 6. LEnormous simple hepatic cysts in children are rare and difficult to diagnose and treat by minimally invasive techniques. Only 14 cases have been reported in the literature, showing female and perinatal predominance. The present report is the 15th case and involved an 18-month-old girl in whom the beak sign on imaging designated a hepatic origin of the cyst. The three-triangular-skin-flap umbilical opening technique enabled aspiration without spillage and laparoscopic complete excision. Complete excision is desirable when feasible because there is a possibility of recurrence or other diseases that require total removal.


Background: Annually, an estimated 20 million (13%) low-birthweight (LBW) and 15 million (11.1%) preterm infants are born worldwide. A paucity of data and reliance on hospital-based studies from low-income countries make it difficult to quantify the true burden of LBW and PB, the leading cause of neonatal and under-five mortality. We aimed to determine the incidence and risk factors for LBW and preterm birth in Lira district of Northern Uganda. Methods: This was a community-based cohort study, nested within a cluster-randomized trial, designed to study the effect of a combined intervention on facility-based births. In total, 1877 pregnant women were recruited into the trial and followed from 28 weeks of gestation until birth. Infants of 1556 of these women had their birthweight recorded and 1279 infants were assessed for preterm birth using a maturity rating, the New Ballard Scoring system. Low birthweight was defined as birthweight <2.5kg and preterm birth was defined as birth before 37 completed weeks of gestation. The risk factors for low birthweight and preterm birth were analysed using a multivariable generalized estimation equation for the Poisson family. Results: The incidence of LBW was 121/1556 or 7.3% : 5.4–9.6%). The incidence of preterm births was 53/1279 or 5.0% (95% CI: 3.2–7.7%). Risk factors for LBW were maternal age ≥35 years , history of a small newborn , and maternal malaria in pregnancy . Intermittent preventive treatment (IPT) for malaria, on the other hand, was associated with a reduced risk of LBW . Risk factors for preterm birth were maternal HIV infection , while maternal education for ≥7 years was associated with a reduced risk of preterm birth  in post-conflict northern Uganda. Conclusions: About 7.3% LBW and 5.0% PB infants were born in the community of post-conflict northern Uganda. Maternal malaria in pregnancy, history of small newborn and age ≥35 years increased the likelihood of LBW while IPT reduced it. Maternal HIV infection was associated with an increased risk of PB compared to HIV negative status. Maternal formal education of ≥7 years was associated with a reduced risk of PB compared to those with 0–6 years. Interventions to prevent LBW and PBs should include girl child education, and promote antenatal screening, prevention and treatment of malaria and HIV infections. Of the 140 million infants born worldwide in 2014, an estimated 20 million 13%) were born with low birthweight (<2.5 kg) [% were boIn 2010, an estimated 15 (uncertainty range 12–18) million preterm infants were born worldwide , In commMultiple maternal and foetal causes of LBW and/or PB  have been described . The ageIn high-income countries, common causes of small birth size include provider-initiated caesarean section and assisted reproduction,  while inTo achieve the sustainable development goal (SDG) 3.2 target of neonatal mortality below 12 per 1000 live births by 2030, there is an urgent need to generate post-conflict context specific data on small newborns’ (LBW and PB) health burden and associated modifiable risk factors. We, therefore, aimed to (1) estimate the incidence of and (2) determine risk factors for low birthweight and preterm birth in post-conflict northern Uganda.This was a cohort study nested within the Survival Pluss cluster randomized trial. The Survival Pluss study assessed the effect of an integrated package consisting of (i) peer support by pregnancy buddies, (ii) provision of mama (birth) kits at household level  and (iii) mobile phone messaging on facility-based births. In the trial, pregnant women were enrolled at ≥28 weeks of gestation and followed up to delivery .The study was conducted in Lira District, Northern Uganda from July 2017 to March 2019. Lira District had a population of about 400,000 people in 2010, dwelling in 13 sub-counties, a city and 751 villages. Lira district was chosen based on its being a post-conflict area with poor maternal and child health indicators, low proportion of health facility deliveries, high neonatal mortality, and limited data on LBW and PBs burden and associated risk factors . The stuA total of 1877 mothers were recruited into the trial at 28 weeks of gestation and followed up to birth. Of these, 1556 mother-infant dyads with birthweight (for LBW burden) and 1279 had both a gestational age estimate using the New Ballard Score (NBS) and birthweight (for PB burden). Only 4 persons conducted the NBS assessment, hence some infants had birthweight (from the clinic or study staff) but not gestational age estimate. The primary outcomes were incidence of (1) low birthweight births and (2) preterm births. Independent or exposure variables were maternal and infant factors. Maternal socio-demographic  and clinical factors  for malaria in pregnancy, history of a small newborn, multiple pregnancy, and antenatal care (ANC) attendance and infant factor (sex), were analysed for association with LBW and PB. A low birthweight (LBW) was defined as birthweight <2.5 kg at birth, while preterm birth (PB) was defined as being born after 28 weeks of gestation but before 37 completed weeks of gestation . We calchttps://opendatakit.org/ (accessed on 6 December 2017)), and the New Ballad Scoring system (NBS) for gestational age assessment. Pregnant mothers were identified by community recruiters who informed the study team. The research assistants were then dispatched to see the identified mothers. Those who met the inclusion criteria were consented and recruited. The enrolled pregnant women were followed up to birth and postnatally to two and seven days, for birthweight and administration of the NBS, respectively. The neonatal anthropometrics (birthweight) and NBS were done within two days and seven days for accurate determination of birthweight and gestation age, respectively. After birth, the same recruiters informed the study team who in turn visited the mother-infant dyads at birth for delivery questionnaire administration and anthropometric  measurements. The weighing scales and length/height boards were calibrated before each field visit and before each measurement was taken. The weighing scales were checked for accuracy daily with known standard weights. Data was collected using standardized pre–coded questionnaires in ODK, and immediately sent to the server for safe custody by the data manager. Data cleaning and checking for completeness were done for quality control throughout the data collection process.Prior to recruitment, research assistants were trained on the study protocol, weight measurement, and electronic data collection tool, the open data kit (ODK) software  and inter-rater  reliability for the Ballard scoring tool were strong. The principal investigator (BO) worked with and supervised the research assistants on data collection and documentation.p value ≤ 0.05 at bivariable analysis were taken into the multivariable generalized estimation equation model with a log link to Poisson family, adjusting for clustering and potential confounding. Known risk factors for LBW and PB such as infant sex, wealth index, and integrated intervention were also added into the final model. The crude and adjusted risk ratios were compared during the multivariable regression analysis. A difference of ≥10% between crude and adjusted risk ratios were considered confounding.The data collected using ODK was sent to a server from where it was downloaded to Stata 14  for analysis. The incidence of LBW and PB were sex standardized and cluster adjusted and presented as the proportion of LBW and PBs to the total number of live births reported in percent  were LBW and of those with gestational age estimate, 4.1% (53/1279) were assessed to be born preterm. Of the LBW infants with gestational age, 19% (20/105) were considered preterm while 37.7% (20/53) of preterm infants were low birthweight .Of the 1556 mother-infant dyads, a quarter of the mothers were first time mothers (prime gravida), 22 (1.4%) were twins, and 90% were married. Most of the fathers were subsistence farmers. Most families used tap or borehole water for domestic consumption. Around 4.4% of the mothers were HIV seropositive, while up to 4.6% did not know their HIV status. Close to 16.9% of mothers had prior history of small newborn in the most recent (second last) delivery. The male to female ratio approximated 1:1, The number of low birthweight infants was 121/1556, 7.7%. The sex and cluster adjusted incidence of LBW in post-conflict northern Uganda was 7.3% : 5.4%–9.6%).The incidence of preterm births assessed by NBS was 53/1279 or 4.1%. The sex and cluster adjusted incidence of PB in post-conflict northern Uganda was 5.0% (95% CI: 3.2%–7.7%). The New Ballard Score being subjective, we analysed in a sensitivity analysis, the effect of potential systematic over–scoring of the maturity rating total score (MRTS) on the incidence of preterm birth . The cruThe factors that were associated with increased risk of a low birthweight infants in our cohort were advanced maternal age (≥35 years), history of a small newborn in prior pregnancy, malaria infection, and unknown malaria status in pregnancy . InfantsHIV infection was associated with an increased risk of PB  in the multivariable analysis . MaternaIn our cohort, the incidence of LBW was 7.3%. The proportion of LBW in post-conflict rural Northern Uganda is lower than most other estimates, be it the global, sub-Saharan Africa, or Uganda ,23,24. TFactors associated with low birthweight included maternal age ≥35 years, history of a small newborn in the previous pregnancy, maternal malaria in pregnancy and intermittent preventive treatment (IPT) for malaria. The finding that advanced maternal age (≥35 years) was associated with an increased risk of LBW in our cohort is not unique to our report. Numerous studies have described the increased risk of LBW with low or advanced maternal age ,26. The The relationship between malaria in pregnancy and its association with increased risk of LBW has been reported elsewhere . SimilarThe preterm birth (PB) proportion in our cohort was 5.0% and is similar to a hospital-based study in Eastern Uganda, with similar inclusion and exclusion criteria . The obsThe low PB proportion observed in our study may be due to the trial eligibility criteria discussed above that could have resulted in exclusion of some preterm births occurring before recruitment into the main trial. Secondly, the NBS for foetal maturation for gestational age determination (instead of mid-pregnancy ultrasound as the gold standard), may have contributed to the underestimation of PB in this cohort. For instance, a study by Sasidharan and colleagues reported that NBS overestimated gestational age (GA) by up to 2 weeks (8 MRTS), with increasing postnatal age . TherefoFactors associated with an increased risk of preterm birth include maternal HIV infection. Maternal education for seven or more years was associated with a reduced risk. Our finding that low maternal education is associated with an increased risk of PB has been reported elsewhere ,32,33. TIn our cohort, teenage motherhood doubled the risk of PB and this is of public health importance. The finding is similar to findings from several other studies across the globe ,36. AlthThe study also reported an increased risk of PB among male infants, compared to female infants. This may be a methodological artefact due to differences in NBS scoring of the two sexes. An analysis of mean difference for the overall MRTS and individual elements for physical and neuromuscular scores by sex, demonstrated a significant difference in physical maturity rating for breasts. Female infants were systematically over-scored by 0.14 (95% CI: 0.08–0.21) equivalent to 4 days (95% CI: 2–6) points in the physical maturity rating for breasts, which may contribute to fewer infants being classified as being PB. It is still possible that there is still true increase in the risk of PB for male infants as this has been reported elsewhere ,41.The main limitation of our study is the potential for selection bias at inclusion which may have introduced systematic error. In the main Survival Pluss randomised trial in which our observational study was nested, inclusions were allowed at any time from 28 or more weeks of gestation (WoG). The inclusion of pregnancies from 28 or more WoG is based on foetal viability in our low resource settings. Deliveries before 28 weeks of gestational age are considered abortions . It means that a pregnant woman could be included at, for instance, 35 weeks of gestation. This also means that not all pregnant women in the study area were followed up from exactly 28 WoG. Women who had LBW and PB before recruitment into the trial were systematically excluded from our study. This likely caused us to underestimate the true incidence of LBW and PB. This could explain the low incidence of LBW and PB reported in this study. Furthermore, additional selection biases could have occurred due to loss to follow up resulting from missing birthweight and/or gestational age assessment (GA) of the infants. For the PB, we restricted the analysis to the sample of infants with both GA and birthweight. Approximately 554 infants (30%) of the 1833 in the cohort did not have both birthweight and gestational age measurements and were excluded from the analysis. This could have possibly resulted in a selection bias. That said, in a sensitivity analysis, we found no major differences in socio-demographic characteristics of included and excluded participants. Future studies to estimate the incidence of LBW and PB should aim at enrolling mothers in the first trimester and following up the entire cohort for the remainder of the pregnancy. This would permit more accurate gestational age estimations and provide a more complete cohort. Albeit the above limitations, there were several strengths in our study. Firstly, we used a community-based cohort—likely to reflect the community at large. Secondly, we were able to follow-up and obtain birthweight within 48 hours on 1556/1833 (85%) of the cohort, minimising the risk of selection bias. Thirdly, mothers were interviewed shortly after the delivery, minimising the likelihood of recall bias. Lastly, we used hard, explicitly defined outcome measures (low birthweight and preterm birth). This reduced the likelihood of misclassification/information bias.The incidence of LBW and PB were low, compared to the national, sub-Saharan Africa and global estimates. Advanced maternal age of ≥35 years and history of a small newborn were associated with increased risk of low birthweight. Maternal formal education for ≥7 years was associated with a reduced risk of PB while HIV infection was associated with an increased risk of PB.


An administrative cohort comprising 40,245 singleton births from 2000 to 2009 in Scania, Sweden, was combined with data on relevant covariates. Investigated sources of PM2.5 included all local sources together as well as tailpipe exhaust, vehicle wear-and-tear, and small-scale residential heating separately. The relationships between these exposures, represented as interquartile range (IQR) increases, and birth weight (continuous) and low birth weight  were analyzed in crude and adjusted models. Each local PM2.5 source investigated was associated with reduced birth weight; average decreases varied by source (12–34 g). Only small-scale residential heating was clearly associated with LBW  per IQR increase). These results add to existing evidence that prenatal exposure to ambient air pollution disrupts fetal growth and suggest that PM2.5 from both vehicles and small-scale residential heating may reduce birth weight.While prenatal exposure to ambient air pollution has been shown to be associated with reduced birth weight, there is substantial heterogeneity across studies, and few epidemiological studies have utilized source-specific exposure data. The aim of the present study was, therefore, to investigate the associations between local, source-specific exposure to fine particulate matter (PM For instance, it was recently estimated that the fossil fuel component of PM2.5 causes 10.2 million premature deaths annually across the globe, or one in five deaths [Humanity’s burning of fossil fuels is not only a key contributor to climate change, but also produces air pollution. Air pollution, derived from both anthropogenic and natural sources, is the largest environmental cause of morbidity and mortality worldwide . AmbientRegarding health effects attributable to air pollution exposure, pregnant women and their developing fetuses may be especially vulnerable. The current evidence of air pollution’s effect on birth weight and low birth weight is quite strong. A review evaluating 84 studies concluded that there were clear associations between maternal exposure to ambient PM and adverse effects on term birth weight and term low birth weight . Conside2.5 in association with birth weight and low birth weight in a low-exposure setting.Studies on source-specific exposure to PM and various health effects, including prenatal exposure on birth weight, are generally lacking due to the historical absence of such detailed exposure data. As source-specific exposure models have now been developed, the aim of the present study was to investigate source-specific ambient PMThe study was conducted in Scania (Skåne) county in southern Sweden, which had a total population of approximately 1.34 million in 2017. We defined an administrative cohort using data on 43,256 singleton births from 2000 to 2009 within the catchment area of hospitals in Malmö, Lund, and Trelleborg.A detailed description of the cohort, Maternal Air Pollution in Southern Sweden (MAPSS), has been previously given elsewhere . To creaThe study population was restricted to women who had given birth during the years 2000–2009 and for whom data on PM exposure and the child’s birth weight was available. We defined the remaining 40,245 singleton pregnancies as our final study population .2.5. The dispersion model was developed using the software program ENVIMAN , a version of the American Meteorological Society/Environmental Protection Agency Regulatory Model (AERMOD) from the United States Environmental Protection Agency [2.5 were modeled for the years 2000 and 2011 at a spatial resolution of 100 m by 100 m. To interpolate the monthly averages between the two modeled years, an atmospheric ventilation index with year- and month-specific meteorological parameters was utilized. This complex method is further detailed in a previous study [2.5 sources could be derived for each 100 m by 100 m grid cell. When validating the modeled PM2.5 values against measurement stations, the R2 varied between 0.44 and 0.86 [A flat, two-dimensional Gaussian plume air dispersion model was used to model concentrations of ambient PMn Agency , which wn Agency . In-deptn Agency . Using tus study . With thand 0.86 .The geographical coordinates of each woman’s residential address, obtained from Statistics Sweden, were linked to MAPSS and used to calculate individual exposure during pregnancy. We replaced pregnancies with missing monthly data with an estimated value based on the mother’s exposure in subsequent years using the expectation-maximization algorithm.2.5; therefore, regional background concentrations, from both naturally occurring air pollution sources and anthropogenic air pollution transported by wind into the area from long distances, were not considered. In Scania, regional background emissions typically comprise the majority of total PM. Thus, investigating local PM yields seemingly low exposure levels. The spatial contrast for regional background concentrations in this study area is low [The focus of the present study was source-specific exposure to locally emitted PMa is low . Because2.5 were investigated: all-source PM2.5, tailpipe exhaust, vehicle wear-and-tear, and small-scale residential heating  were very small. Thus, these were not examined separately but are represented in the all-source PM2.5 category. The distributions of the exposure variables are seen in Four sources of locally emitted PM heating . PM2.5 fThe outcome variables in this study were birth weight  and low birth weight . For the latter, the World Health Organization’s (WHO) definition of LBW (<2500 g) was employed .The risk factors considered were maternal age , parity , pre-pregnancy body mass index , smoking status at first antenatal visit , fetal sex , birth year (2000–2009), and birth month from PRS. Additionally, we incorporated data from Statistics Sweden on individual socioeconomic status, namely, maternal education  and annual household disposable income (quartiles). Information on gestational length in days, estimated from ultrasound scans during pregnancy, was also available from PRS; extreme values (<175 days and >300 days) were coded as missing. Neighborhood-level socioeconomic status was included using a measure defined by Statistics Sweden as the proportion of inhabitants in the neighborhood with “low economic standard” based on income levels [2.5 sources  served as the outcome of interest. When considering low birth weight (dichotomous), binary logistic regression was applied. Here, cases were defined as LBW babies and controls as non-LBW babies. Associations between locally produced PM2.5 and both outcomes were investigated using crude and adjusted models; the latter of which adjusted for the effects of maternal age, parity, pre-pregnancy BMI, smoking status, education as categorical variables, annual household disposable income (continuous variable), and sex of the child.Due to high correlations between local PM sources , we utilIn separate sensitivity analyses, additional covariates were added to the adjusted model. The first is adjusted for birth year and birth month. Birth year was included to account for both annual variation in long-distance, in-transported air pollution and potential trends in diagnostic procedures. Birth month was utilized to adjust for seasonal variations in air pollution emissions from, for example, wood-burning and studded-tire use not captured by the exposure models, as well as other seasonally varying potential confounders, such as vitamin D . The sec®, Armonk, NY, USA). Results for the linear and logistic regressions are reported as the absolute change in birth weight (grams) and odds ratios (OR) for low birth weight, respectively. A significance level of 0.05 was used in all analyses, yielding 95% confidence intervals (CIs).All statistical analyses were carried out using SPSS version 27 .2) was correlated with low birth weight, but a pattern was less clear for the remaining BMI categories. Regarding parity, trends were not consistent; however, some differences were seen, such as a higher probability of low birth weight if parity was 1 or ≥4.The relationships between the outcome variables and covariates are detailed in 2.5 exposure in relation to birth weight and the covariates .Considering PMvariates , concent2.5 and birth weight , 33 g (95% CI: 25–41), and 12 g (95% CI: 5–19), respectively.The results demonstrated clear associations between each investigated local source of ambient PMh weight . Birth w2.5 in the crude model, with an OR of 1.16 (95% CI: 1.04–1.30), was observed  and an adjusted OR of 1.14 (95% CI: 1.04–1.26).For LBW, an association with all-source ambient PMobserved . In the When tertiles were used instead of linear exposure variables, the confidence intervals for the estimates were generally very wide, but most of the estimates seemed to suggest that it was reasonable to assume linear associations (data not shown).2.5 from small-scale residential heating to become slightly more attenuated when adjusting for birth year and birth month, and the precision decreased, with an OR of 1.09 (95% CI: 0.98–1.23). In the analysis where preeclampsia was added to the adjusted models, the average reduction in birth weight was 34 g (95% CI: 25–42) for each IQR increase in all-source PM2.5, which is comparable to the 34 g (95% CI: 26–43) decrease found when preeclampsia was not included. In line with this, the estimates of the LBW analyses were not affected by adding preeclampsia into the statistical models (data not shown). The final sensitivity analysis utilizing mixed models, furthermore, had only a marginal effect on the estimates (data not shown).The sensitivity analyses incorporating birth year and birth month, gestational days, and neighborhood-level socioeconomic status had generally little influence on the effect estimates . However2.5 stemming from traffic-related sources as well as from small-scale residential heating, which is mainly attributable to wood-burning in this setting. Furthermore, the risk of low birth weight (<2500 g) was seen to increase with increasing exposure to PM2.5 from small-scale residential heating.In this administrative cohort study from southern Sweden, we observed statistically significant associations between exposure to ambient, locally emitted particulate air pollution during pregnancy and birth weight for PM2.5 from small-scale residential heating and LBW. While this may imply some residual confounding due to temporal trends in the distribution of exposure or potentially confounding factors, such yearly or seasonal variations are an unlikely explanation of the findings. Still, this may partly contribute to the increased risk for LBW associated with PM2.5 from small-scale residential heating.The sensitivity analysis adjusting for birth year and birth month resulted in slightly attenuated ORs for the association between PM2.5 emissions is very low in our study setting  and, therefore, typically accounts for quite a small proportion of the total PM2.5 concentrations. For example, the mean local concentration of all-source PM2.5 was 1.41 µg/m3, while the total concentration of PM2.5 in Malmö, a major city within the study area, averaged around 10 µg/m3 between 2016 and 2020 [3 annual mean, but still do not meet the WHO’s recently revised, stricter air quality guidelines of 5 µg/m3 annual mean [Interestingly, we observed statistically significant associations even though the local contribution to PMand 2020 . Moreoveual mean .2.5 from traffic, organic and oil combustion, and secondary sulfates during pregnancy [2.5 exposure from secondary ammonium sulfate, secondary ammonium nitrate, and suspended oil during pregnancy increased the risk of term low birth weight [3) in exhaust particles during the entire pregnancy. The effect size was, thus, smaller than in the present study, where a 33 g (95% CI: 25–42) reduction in birth weight for each IQR increase (0.12 µg/m3) in PM2.5 from tailpipe exhaust was seen. These differences are interesting and difficult to explain, as the two studies are similar in many respects. For example, both are register-based, Swedish studies using similar exposure assessment methods. However, the Stockholm study adjusted tailpipe exhaust particles for ozone and paternal education.It is well established that maternal smoking during pregnancy reduces birth weight  and incrregnancy . Anotherh weight . Similarh weight . The aut2.5 from both vehicles and small-scale residential heating, and birth weight, therefore, add to these previous findings.It has furthermore been suggested that exposure to indoor air pollution from wood-fueled cook fires may affect birth weight through the same mechanisms as environmental tobacco smoke . Indoor 2.5 and low birth weight are not well known. Oxidative stress and chronic systemic inflammation triggered by air pollution exposure are thought to play a role in fetal development and growth as well as placental function, which, in turn, affect a baby’s birth weight [2.5 [2.5 exposure during pregnancy and birth weight.The underlying biological mechanisms driving the association between PMh weight . In addight [2.5 . Many epght [2.5 ,27, whicght [2.5 . Preecla2.5 from small-scale residential heating (mainly wood-smoke in the present study), but not other investigated PM2.5 sources, and an increased risk of LBW. This may imply differences in chemical composition and toxicity among the air pollution sources. There is growing evidence of the detrimental health effects of wood-smoke. Human chamber studies, for example, have suggested wood-smoke exposure to be associated with increased arterial stiffness and decreased heart rate variability [2.5 from small-scale residential heating was not statistically significant in the present study, and even attenuated when adjusted for birth month and birth year, this particular result should be interpreted with caution. Moreover, such associations should be interpreted and investigated by other experts in the field, as additional research is needed to corroborate this finding.The results indicated an association between PMiability . Additioiability . Five ofiability . Howeveriability . Given tThe importance of normal birth weight has been established through numerous studies that underscore its contribution to physiological and psychological development throughout one’s life ,34,35,36Additionally, our results are in line with a growing body of research suggesting that locally emitted air pollution has more severe health effects than regional, background air pollution , which t2.5 from both tailpipe exhaust and vehicle wear-and-tear in the present study, the correlation between these two sources was very high  and the detailed maternal PM2 varied between 0.44 and 0.86. This proportion of variation could be considered acceptable; however, 56–14% of the variation remains unexplained by the exposure models in the present study. It would, furthermore, have been desirable to adjust for ozone and paternal education as potential confounders in our study, but no reliable data was available. A weakness in all studies on ambient air pollution that assess exposure at the residential address is that this outdoor concentration of air pollutants is a poor indicator of actual personal exposure; therefore, exposure misclassification can be present [Despite its strengths, our study also has limitations. First, there is a measurement error in the modeled concentrations of air pollution. When these were validated against values from measurement stations, the R present . Even th2.5 from both traffic-related sources and small-scale residential heating (mainly wood-burning) contribute to this association. Furthermore, our results identify an association between local PM2.5 from small-scale residential heating and low birth weight (<2500 g). This suggests that the ambient emissions from, and subsequent health impacts of, wood-burning should not be overlooked by policy makers when planning for climate change mitigation and air quality improvement at the local level. Overall, these findings strengthen the existing literature, demonstrating that adverse health effects of exposure to PM2.5 from local emission sources occur even in low-exposure areas.The present study adds to current evidence that ambient exposure to air pollution during pregnancy reduces babies’ birth weight and indicates that locally produced PM


Among those, n = 885 warmed blastocysts were cultured for 2–4 h, and n = 1029 were kept in culture for 20–22 h prior to transfer; the remaining blastocysts did not survive the warming protocol. We observed no significant differences in live birth and clinical pregnancy rates between the two groups. The blastocyst morphological evaluation at transfer improved following the longer culture time. No differences between the two groups were found also for gestational and neonatal outcomes. This work shows that different post-thaw embryo culture timings do not negatively impact pregnancy outcomes. Overall, these results are important in the context of the embryological laboratory in order to better organize the workflow and avoid unnecessary timing-related workload.The frozen embryo transfer (FET) technique has been progressively used more worldwide due to improved culture conditions, as well as enhanced survival rates after vitrification. However, little is known about the effect of the post-thaw blastocyst culture duration prior to transfer on live birth rate in FET cycles. In this retrospective observational study, we evaluated the influence of two distinct post-thaw blastocyst culture spans (2–4 h versus 20–22 h) on clinical pregnancy and live birth rate. A total of  In recent decades, assisted reproduction technology (ART) treatments have been enormously shaped by the advancement of cryopreservation methods, leading to widespread use of the frozen embryo transfer (FET) strategy . Frozen Here, we demonstrate the influence of a short (2–4 h) and long (20–22 h) post-thaw culture period on day 5 blastocysts prior to transfer. Specifically, we confirm that FET can be efficiently carried out after either a short or long day 5 blastocyst culture duration, followed by similar results in terms of clinical pregnancy and live birth rates.This retrospective study was conducted at the Infertility Center—Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan between 2014 and 2021. We included couples with IVF indications who underwent frozen–thawed blastocyst transfer either after a freeze-all strategy or for supernumerary embryos. Only transfer of single blastocysts vitrified at day 5 and warmed were evaluated. The choice on the timing of blastocyst culture after thawing was based essentially on the workload and organizational preferences of the embryologists and not on clinical or embryological parameters. We primarily compared the live birth rate of patients undergoing FET after a short blastocyst culture time (2–4 h) prior to transfer to that of patients in whom thawed blastocysts were transferred after a long embryo culture time (20–22 h). The secondary outcomes of the study were clinical pregnancy and miscarriage rates. Clinical pregnancy rate was defined by the presence of at least one intrauterine gestational sac, assessed by the sonographic documentation, divided by the number of embryo transfer cycles for each group, while miscarriage rate was defined as a spontaneous loss of pregnancy before the 12th week of gestation divided by the number of clinical pregnancies for each group. In accordance with Italian law, all pregnant women were followed up with, and pregnancy and neonatal data, including rates of hypertension, gestational diabetes, placenta previa, preterm birth (birth of an infant before 37 completed weeks of gestation), and low birth weight (LBW—defined as a birth weight of fewer than 2500 g) were precisely collected. The local Ethics Committee Milan Area 2 approved the research protocol .Controlled ovarian stimulation was performed after assessing age, day 3 serum FSH, serum anti-Mullerian hormone (AMH), and antral follicle count (AFC) in order to define the proper gonadotropin type to be used, as well as the starting dose . All patIn our laboratory, a shared embryo quality control, as well as other subjective assessments among the embryologists, is undertaken with a biannual frequency in order to standardize the evaluations. In any case, the quality of the embryos has been generally evaluated by the same embryologist (head of the lab) who is assigned to this specific task.After 5 days of culture, blastocyst evaluation was performed according to the Istanbul Consensus . In lineWomen with frozen blastocysts were scheduled for a natural cycle if they reported having regular menstrual cycles and a mean cycle length between 24 and 35 days. Eligible women were monitored with sequential transvaginal ultrasounds starting from day 6–9 of the cycle, and a luteinizing hormone (LH) surge assessment was achieved by monitoring urinary sticks for an LH surge three times per day  until the leading follicle reached 16 mm. Four days after the LH surge (+3 from presumed ovulation), women underwent a transvaginal ultrasound and serum progesterone assessment. Embryo transfer was performed 6 days after LH surge (+5 from presumed ovulation). No luteal phase support was given. Hormone replacement treatment (HRT) was prescribed if women had irregular menstrual cycles or if the monitoring of the natural cycle failed. Specifically, they received daily 4 mg of estradiol valerate orally from day 2 of the cycle that was increased to 6 mg after 6 days. The dose was further increased to 8 mg if the thickness of the endometrium did not reach 7 mm. Progesterone was then introduced progressively, reaching the plateau  after two days  . Single-Blastocysts were warmed using the thawing kit   and cultp values below 0.05 were considered statistically significant. A binomial distribution model was used to calculate the 95% confidence interval (95% CI) of proportions. A logistic regression model was used to calculate the adjusted odds ratio (OR) of pregnancy and live birth. Variables included in the model were age and number of oocytes retrieved. The sample size was calculated in order to demonstrate that the transfer of frozen–thawed blastocysts after a long embryo culture (20–22 h) could lead to a relative reduction of the live birth rate probability ≤ 20% (from 30 to 24%). Setting type I and II errors at 0.05 and 0.20, respectively, a sample size of n = 860 blastocysts for each group was deemed appropriate.Data were analyzed using the SPSS software 27.0 . The Fisher exact test, chi-squared test and Wilcoxon’s test were used as appropriate, and n = 1927 day 5 blastocysts FET cycles, of which n = 885  warmed blastocysts were cultured for 2–4 h (short culture), and n = 1029  were kept in culture for 20–22 h (long culture) prior to transfer; the remaining 13 blastocysts  did not survive the warming protocol.Between 2014 and 2021, we analyzed a total of The basal characteristics of the patients who underwent FET cycles with the short and long blastocyst culture were similar . The medn = 5 (0.5%) belonged to the short-culture group and n = 8 (0.7%) to the long-culture group. No statistically significant differences were found between the short- and long-culture groups in live birth rate after FET , suggesting that the distinct culture duration prior to blastocyst transfer does not negatively impact the main ART goal (p = 0.06)  . The OR We have also assessed blastocyst morphological features. At vitrification, 28 (3%) and 66 (6%) of blastocysts were early blastocysts (grade 1), 335 (38%) and 549 (54%) were blastocysts (grade 2), 515 (58%) and 412 (40%) were fully expanded (grade 3), and 7 (1%) and 2 (<1%) were hatched (grade 4) in the short- and long-culture groups, respectively. Even if blastocysts, that were transferred following a short culture post-warming, displayed a significantly superior morphology at the vitrification moment, those that were warmed the day before  displayed a significantly improved morphology at transfer .A higher number of less-expanded blastocysts at vitrification were cultured for a longer period. On the other hand, independent from the original expansion, blastocysts seemed to benefit more from a longer culture. In this group, trends toward a higher live birth rate and a significantly higher clinical pregnancy rate were observed for blastocysts that, at vitrification, were at grades 1–2 or 3–4 of expansion, respectively.To gather more knowledge on the influence of blastocyst culture duration on the most relevant ART outcomes, we subsequently assessed pregnancy and neonatal outcomes after transfers of single warmed blastocysts vitrified at day 5. Rates of spontaneous abortion, ectopic pregnancy, intrauterine fetal death, gestational diabetes, hypertension, placenta previa, preterm labor, low birth weight babies, per blastocyst transferred, were found to be similar between the short and long culture group .Overall, our findings demonstrate that different culture timings after warming of day 5 blastocysts have similar ART clinical outcomes. Specifically, in terms of clinical pregnancy and live birth, no differences were noticed between the short-(2–4 h) and long-culture (20–22 h) groups. Therefore, both culture approaches may be efficiently applied, and the decision would be based on the laboratory workflow.The use of frozen embryo transfers has steadily increased over the past decade, and this approach to ART is now practiced worldwide . This stThe interaction between the blastocyst hatching and endometrial receptivity is critical for implantation, although it is challenging to accurately establish the level of synchronicity needed for a successful outcome . To someOn the other hand, we decided to limit this study to blastocysts vitrified on day 5 in order to contain biases related to critical embryological aspects. Indeed, according to some studies, the live birth following frozen–thawed blastocyst transfer was significantly lower with day 6 than with day 5 blastocysts, regardless of their quality ,26. EmbrIn terms of blastocyst quality, we have observed an improvement in the number of top-quality blastocysts following the long culture period. This observation is in line with previous reports  and is lIn regard to obstetric and neonatal outcomes, we did not find any significant differences in terms of spontaneous abortion rate and ectopic pregnancies between the studied groups. Similarly, no differences were found for maternal adverse outcomes and birth weight. Overall, these data appear to indicate that there is no effect of the interval between blastocyst thawing and transfer on these outcomes.Some strengths and limitations of this study deserve to be commented on. The sample size of this study represents a strength as it allowed us to detect a relative reduction in the live birth rate of at least 20% in association with the long culture period. We could not detect any reduction in ART outcomes following this approach. Moreover, given the use of common protocols for both blastocyst freezing and warming, the generalizability of the results is likely to be solid. Among the limits, we were not able to report the quality of day 3 embryos from which each blastocyst was derived since we commonly use a grouped-embryo culture strategy. However, this parameter does not seem to be critical in the context of this study . As mentOur results revealed that both short and long blastocyst culture durations guide proper day 5 blastocyst expansion, development, and competence, thus leading to successful and comparable ART outcomes. These results are critical for the organization of workflow in the IVF laboratory. However, randomized trials are required to confirm the present findings.


Women and infants are among the most vulnerable groups for micronutrient deficiencies. Pregnancy micronutrient status can affect birth outcomes and subsequent infants’ growth.We determined the relationship between maternal iron and vitamin A status at delivery using several biomarkers  and birth outcomes  in rural Uganda. We investigated women who had serum results at the point of delivery and paired them to their infants at birth (n = 1244). We employed multivariable linear and logistic regression, adjusting for clustering at the subcounty level to determine the relationship between maternal micronutrients and birth outcomes.p < 0.030).After adjusting for relevant factors, we found that maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with the assessed birth outcomes. However, there was a significant association between serum sTFR and preterm births . For Vitamin A, we observed a significant positive association between RBP and length-for-age (LAZ) at birth (β = 0.12, These findings indicate that the relationship between maternal iron status and birth outcomes needs to be further investigated, because depending on the biomarker used the associations were either in favor of an adverse birth outcome or not significant. Additionally, they confirm that higher maternal RBP levels could be beneficial for birth outcomes.Clinicaltrials.gov as NCT04233944.The online version contains supplementary material available at 10.1007/s10995-022-03387-5. There is conflicting evidence of the different types of biomarkers used to assess maternal micronutrients status (in this case iron and vitamin A) and their relationship with birth outcomes. Our study aims to address this question by using the three major indicators of iron status  and RBP for vitamin A status, in a relatively large sample of mothers in rural Uganda. In addition, to achieve more precise estimates, we correct for inflammation using C-Reactive Protein (CRP) and α-1 acid glycoprotein (AGP) as per suggested in the most recent literature.Women and infants are among the most vulnerable groups for micronutrient deficiencies CDC, . Iron anDifficulties arise when assessing micronutrient deficiencies in countries where a high burden of infection exists because biomarkers used to measure them are triggered by inflammation  and birth outcomes  after adjusting for relevant factors in rural Uganda. A second objective was to describe the prevalence of iron and vitamin A deficiencies, anemia, and IDA in this population of mothers with and without adjusting for inflammation using the BRINDA correction.The Uganda Birth cohort (UBC) study was a longitudinal prospective birth cohort of pregnant women aged 15–49 years from rural North and South-Western subcounties (geographic administrative units) of Uganda. Funded by the United States Agency for International Development (USAID) the UBC was conducted between 2014 and 2016. The aim was to intensively study pregnant women, their children and households to understand the impact of agriculture, nutrition and health interventions provided by the Uganda Community Connector project (CC) USAID, . PregnanOf the women enrolled, data from 4949 were available by Visit 1. Women and their infants were followed throughout the first year of the child’s life. Data were collected at enrollment, birth Visit 3), and at 3 (Visit 4), 6 (Visit 5), 9 (visit 6) and 12 (Visit 7) months from the date of delivery  of Makerere University School of Public Health, and the Institutional Review Board (IRB) from both Tufts Health Sciences and Harvard T.H. Chan School of Public Health. The UBC study was registered at clinicaltrials.gov as NCT04233944.In this paper, we investigated a subsample of women who had serum sample results at the point of delivery and paired them to their infants measured within 72 h of birth n = 1244) to assess the relationship between biomarkers and birth outcomes  were drawn at the point of delivery , and the resultant serum was frozen and shipped to US and Germany for processing, distribution and analysis. The VitMin Lab in Germany analyzed ferritin (FER), sTFR, RBP, and inflammatory markers C-Reactive Protein (CRP) and α-1 acid glycoprotein (AGP) using a sandwich enzyme-linked immunosorbent assay  =  − [log(sTFR/FER ratio) − 2.8229]/0.1207  using their regression correction approach , preterm births, WAZ, LAZ, WLZ and head circumference. Birth weight (kg) was measured using a Seca 874 digital scale (accuracy ± 50 g) and calculated as the mean of three repeated measurements on each infant (Seca Corporation). Length was measured using a measuring board (accuracy 0.1 cm) (Infant/Child/Adult ShorrBoard®). LBW was defined as the percentage of infants with birth weight lower than 2500 g. Gestational age (days) was calculated as the date from last menstrual period to delivery date. Implausible gestational ages  were excluded from analyses (n = 150). Two outcome variables were derived from gestational age: preterm birth and SGA. A preterm birth was defined as gestational age < 259 days  were calculated using infant’s age, weight and length variables at birth. Birth lengths less than 45 cm were excluded from the WLZ calculation. Other exclusions included WAZ <  − 6 or > 5, WLZ <  − 5 or > 5, and LAZ <  − 6 or > 6. Stunting, underweight and wasting were defined as LAZ, WAZ and WLZ less than − 2 standard deviations respectively. Head circumference (cm) was measured using a tape and computed as a mean of three different measurements on each child at birth.The primary exposure variables included ferritin, sTFR, BIS, hemoglobin and RBP. Other covariates included Wealth Index, food security as measured by the Household Food Insecurity Access Scale (HFIAS)  and folic acid tablets is recommended in Uganda throughout pregnancy  standardized scores for WAZ (underweight), LAZ (stunting) and WLZ (wasting) were − 0.1 (± 1.1), − 1.0 (± 1.7), and 0.6 (± 1.7), respectively. The mean (± SD) gestational age at birth was 274 days (± 22) and 14% of the infants were born SGA. About 20% of all infants were born preterm. The mean (± SD) gestational age of those born preterm was 240.8 days (± 16.4) and at term, 282.7 days (± 13.3). Their range of gestational ages was 168–258 days and 259–315 days, respectively.Table The prevalence of iron and vitamin A deficiencies and anemia in Ugandan mothers is depicted in Table To describe RBP values as a proxy for vitamin A deficiency, we used the recommended cut-off for retinol (RBP < 0.7 µmol/L) WHO, . Some stResults for the associations between maternal iron and vitamin A biomarkers and birth outcomes are shown in Tables Maternal iron status (ferritin and BIS) and anemia (hemoglobin) were not significantly associated with any of the assessed birth outcomes. However, all things considered, higher sTFR levels, indicative of iron deficiency, were associated with a 33% decrease in the odds of delivering a preterm baby . We further tested for influential points using Cook’s distance and identified 75 observations that may have an effect on the relationship between sTFR and preterm birth. Upon omitting them, the significant relationship remained significant .p < 0.030). The bivariate relationship and its magnitude is shown in Fig. p < 0.0046).Regarding vitamin A status Table , we obseThis study found no relationship between ferritin or BIS and birth outcomes, but it did observe an association of lower risk of preterm births and higher levels of sTFR, an indicator of iron deficient erythropoiesis. These results are in line with recent findings in China, Papua New Guinea and Taiwan  found in this study could be explained by the high percentage of IPT use (82%). This treatment, accompanied by other preventive interventions, is a product of national and international programs to reduce malaria in Uganda over the past decade. The prevalence of anemia (14%) was also lower compared to that reported in another study (29%) Below is the link to the electronic supplementary material.