Studies found that maternal education is the most frequently assessed predictor of child’s birth weight. Lower level of education was consistently found as indicator of lower child’s birthweight. In turn, inequalities in child’s birthweight have been repeatedly shown to be closely related to inequalities in later adult health. The aim of this project is to evaluate the association between the highest achieved level of maternal education and birthweight of single born babies in large English and Welsh population sample, taking into account factors such as child’s gender, parity, maternal age, partnership status, ethnicity, and household socioeconomic characteristics.Using Office for National Statistics Longitudinal Study (ONS LS) based on English and Welsh Census data, information from almost quarter of a million children born since 1981 to ONS LS sample mothers were used. Maternal education was categorised in 3 categories , and its association with child’s birth weight was analysed by logistic regression accounting for range of available covariates.Significant association between the level of education and birth weight was found in crude analysis (p < 0.001). When adjusted, the magnitude of the association with education gradient declined but remained highly significant and was found to considerably increase over the years. The birth weight difference between those born to mothers with below secondary education and those born to mothers with degree increased by more than 60 grams (p for change <0.001) between 1981 and 2016.These findings support previous evidence based on different population samples. According to our results, children of mothers with below secondary education tend to have lower birth weight. Our results suggest that the inequalities in birth weight by the highest education level achieved by mother significantly increased since 1981.• Lower levels of maternal education predict low birth weight in children.• The differences in birth weight by maternal educational demonstrate increase in inequalities over the years.


Kit survival in the first hours after farrowing has been related to the birth weight of kits. In prolific species, newborn survival is controlled both by the genes of the newborns that are involved in vitality, health, and growth (direct genetic effects), and by the dam effects that affect milk yield and other mothering abilities . Genetic parameters of peri and postnatal survival have been estimated traditionally on the performance of dam , but it is more appropriate to consider as categorical traits of the kit. The objective of this study was to estimate the heritabilities of kit survival at birth and weaning, as well as the individual birth weight, and the genetic correlations between those survival traits and birth weight using a combined linear threshold model with a Bayesian approach. Heritabilities of survival at birth and weaning, as well as birth weight, were low (0.021 and 0.027) for survival traits and slightly greater (0.146) for birth weight after adjusted litter size. No genetic correlation was found between survival traits. Genetic correlation between survival at birth and birth weight showed a positive value (+0.134 and +0.535 after being adjusted for litter size). These magnitudes of genetic parameter estimates suggested that there is substantial potential for the genetic improvement of kit survival at birth through selection for birth weight.Genetic parameters of kit survival traits and birth weight were estimated on ITELV2006 synthetic line aimed at improving kit survival using a multiple trait linear and threshold model. Data on 1696 kits for survival at birth and at weaning, as well as individual birth weight and litter size were analysed. Genetic effects of kit survival traits and birth weight were estimated based on threshold and Gaussian models, respectively, using a Bayesian approach. The statistical model included, as fixed effects, parity, lactation status, season of farrowing, nest status, cannibalism in kit, place of kit’s birth in the cage and gender, and adjustment for litter size. Posterior means of heritabilities for direct genetic effects of survival at birth and the entire nursing period, as well as birth weight, were 0.018, 0.023, and 0.088, respectively, and were increased when adjusted for litter size to 0.021, 0.027 and 0.146. Genetic correlation between survival traits was zero. Therefore, these traits can be treated genetically as different traits. Genetic correlation between direct effects of survival at birth and birth weight showed positive, but low, value (+0.134) and was increased to +0.535 when the traits were adjusted for litter size. No genetic correlation was found between survival at weaning and birth weight. These magnitudes of genetic parameter estimates suggested that there is substantial potential for the genetic improvement of kit survival at birth through selection for birth weight. The number of weaned kits per dam is the main driver of the profitability of rabbit meat production . TherefoIn prolific species such as pigs and rabbits, newborn survival is controlled both by the genes of the newborn that are involved in vitality, health, and growth (direct genetic effects), and by the dam effects that affect milk yield and other mothering abilities , which is a challenge for improving newborn survival genetically . GeneticThis study was approved by the scientific council of the Biotechnology Laboratory of Animal Reproduction, part of the Institute of Veterinary Sciences at the University of Saad Dahleb Blida .The animals came from the ITELV2006 synthetic line. This line was created as part of a co-operative rabbit project between the Institut Technique des Elevages  and Institut National de la Recherche Agronomique  by means of inseminating does from a local Algerian rabbit population with the semen of bucks from the INRA2666 synthetic line . The ITEDoes and bucks were individually housed in wired flat-deck cages in a building equipped with a cooling system. They were kept under a consistent photoperiod of 16L:8D (light:dark hours). Animals were fed a standard commercial pelleted diet ab libitum  and had free access to water. Natural mating was performed. Adult males (7–10 months of age) were used. A maximum of two matings per week were carried out, and the same feeding protocol was used throughout the experiment, in order to qualitatively and quantitatively guarantee the quality of the semen. Does were mated first at 20 weeks of age and at 10 d after parturition. If the does refused to be mated, they were again mated a week later. This implies that some of the does carried out gestation and lactation at the same time.Three days before parturition, nests were placed into the cages. Every morning, after 8 am, all the nest boxes were revised, and status of the nest, presence of cannibalism in kits, and if kits were born inside or outside of the nest was recorded. Assessment of nest quality was based on presence of doe’s hair in the nest  as described by Blumetto et al. . Kits bob included the systematic effects of parity , lactation status (lactating and non-lactating doe at mating), season of farrowing (summer and autumn), nest quality , cannibalism in kit (yes or not), born inside of the nest (yes or not) and gender of kit. The vectors a, m, c and e represent the direct additive genetic effects of the kits, maternal permanent environmental and common litter effects of the does and the environmental residual effects, respectively. X, Z, W and V are incidence matrixes linking the effects with y. In further analyses, survival at birth and weaning and individual birth weight were additionally adjusted for number of kits born in order to to assess the influence of litter size on the estimates.The traits analysed were survival at birth (SB), survival at weaning (SW), and individual birth weight including dead kits (BW). In the genetic analyses, survival traits were coded as one (dead) and two ; zero was interpreted as a missing value. Dead kits at birth were treated as missing observations in the trait survival at weaning. Multiple trait Bayesian analyses were carried out using a threshold model for survival traits and a linear Gaussian model for birth weight. The multiple trait animal model is as follows:A and I are the additive genetic relationship matrix and identity matrix, respectively. G0 represents the variance and covariance matrix of the direct additive genetic effects of the kits and has the following structure:The variance–covariance structure was:M0 represents the variance and covariance matrix of the maternal permanent environmental effects and has the following structure:C0 represents the variance and covariance matrix of the common litter effects and has the following structure:R0 represents the variance and covariance matrix of the residual environmental effects and has the following structure:Bayesian analyses were carried out using Gibbs sampling in order to estimate the variance components of survival traits and individual birth weight. In these analyses, bounded uniform priors were used for the systematic effects with:The conditional prior distributions for the additive genetic, maternal litter and residual environmental effects were sampled from a multivariate normal (N) distribution withStatistical inferences were derived from samples of the marginal posterior distribution obtained by Gibbs sampling as implemented in the program TM . The herThe mean birth weight, including dead kits, was 1.43 g lower and 1.05 g higher standard deviation than those excluding weights of dead kits. Losses occurring at birth were similar to during the entire nursing period  compared with survival traits . These hGenetic correlation between direct genetic effects of survival at birth and at weaning was small −0.111,  and not Apart from the correlation between survival at birth and at weaning, adjustment for litter size resulted in an increase in correlation among birth weight and survival traits (+0.535 for survival at birth and +0.083 for survival at weaning, The phenotypic fractions of the maternal permanent environmental variance for survival traits and birth weight (0.024 to 0.070, The phenotypic fractions of the variances common to all kits within a litter were 0.199 for survival at birth, 0.234 for survival at weaning and 0.435 for birth weight , substanThe present study shows that 20% of kits born perished before weaning, which is in the range values of those published in maternal rabbit lines by García and Baselga  and BadaSuccess of selection for improved kit survival depends on that trait having variability and being heritable. Kit survival traits presented moderated variability in this study, e.g., coefficients of variation ranged from 25 to 27%. In relation to heritability, it should be noted that genetic parameters for newborn survival traits in prolific species such as pigs and rabbits have mainly been estimated by treating survival as a trait of the dam using, for example, number of stillborn or its proportion of the number born ,9,10. InThe genetic correlations between direct genetic effects of survival traits were near zero. Consequently, these peri and postnatal survival traits can be treated genetically as different traits. Our results agree with the low genetic correlation between direct effects of piglet survival at birth and during the nursing period reported by Roehe et al. , Lund etThe results of the present study showed that kit survival at birth and during the nursing period is under genetic control, but the low heritabilities would limit the success of selection. Birth weight displayed a positive genetic correlation with kit survival at birth and a higher heritability than survival traits. Therefore, selection for birth weight could be a useful tool for the improvement of kit survival at birth. However, further studies on this species are required to validate our results.


Neurodevelopmental disorder (NDD) in preterm infants has become of great interest. We aimed to investigate the impact of preterm birth on the proportion of NDD using nationwide data provided by the Korean National Health Insurance Service. We included 4894 extremely preterm or extremely low-birth-weight  infants, 70,583 other preterm or low-birth-weight  infants, and 264,057 full-term infants born between 2008 and 2015. We observed their neurodevelopment until 6 years of age or until the year 2019, whichever occurred first. Diagnoses of NDDs were based on the World Health Organization’s International Classification of Diseases 10th revision. An association between preterm birth and NDD was assessed using a multivariable logistic regression model. There was a stepwise increase in the risk of overall NDD with increasing degree of prematurity, from OP/LBW , to EP/ELBW . The EP/ELBW group was strongly associated with developmental delay , cerebral palsy , and autism spectrum disorder . Preterm birth considerably increased the risk of NDD by the degree of prematurity. Recent advances in neonatal care have led to a marked increase in the survival rate of preterm infants. According to the Korean Statistical Information Service in 2020, preterm birth  < 37 weeks) and low birth weight  accounted for 8.6% and 6.8% of total births, respectively, both of which were markedly higher than the figures for a decade ago, 5.8% and 4.9% . As the Neurodevelopmental disorder (NDD) is a group of lifelong conditions characterized by impairments in cognitive, communication, behavior, and motor skills . GrowingAs a definition of neurodevelopmental impairment varies across the nations or cohorts, definitions used in the study significantly influence the probability of NDD at diverse ages . For insHerein, we investigated the overall prevalence of NDD in preschool-age children who were born prematurely, stratified by demographic and socioeconomic characteristics, using the nationwide database provided by Health Insurance Review and Assessment Service (HIRA) in South Korea.We used the database obtained from the HIRA. The HIRA stores and reviews data on medical claims for the South Korean population, including diagnostic codes, medical visits, prescription records, and demographic information. In South Korea, each individual is registered with his/her health insurance identification number. More than 97% of the population is covered by national health insurance, and the remaining population is covered by the medical-aid program that provides healthcare services to low-income households. Thus, medical-aid beneficiaries can be defined as having the lowest socioeconomic status. Records with diagnostic codes were based on the World Health Organization’s International Classification of Diseases 10th revision (ICD-10). The study was approved by the Institutional Review Board of Hanyang University (IRB No. 2020-08-031). Informed consent was not required since public data from the HIRA were used.We analyzed health claims data of the pediatric population with ICD-10 birth codes recorded between 2008 and 2019 in the HIRA database. Our study population included newborns from 2008 to 2015 and observed their NDD until six years of age or until the year 2019, whichever occurred first. Since the database contain missing data in the ICD-10 birth codes for GA or birth weight, the study population was subdivided into three subgroups combining these measures; (1) EP or extremely low-birth-weight (ELBW) infants, with GA < 28 weeks or birth weight < 1000 g; (2) other preterm (OP) or LBW infants, with GA < 37 weeks or birth weight < 2500 g; and (3) full-term infants (FT), infants with GA ≥ 37 weeks. Exclusion criteria were as follows: (1) children diagnosed with congenital malformations of the nervous system , (2) children diagnosed with chromosomal anomaly (Q09); and (3) children with missing information for GA or birth weight.The NDDs of interest included developmental delay (DD), cerebral palsy (CP), ASD, ADHD, LD, ID, and tic disorder (TD). Detailed information about ICD-10 codes for the definition of the study group and each sub-condition is summarized in The annual cumulative incidence of each sub-condition was calculated starting on the 1 January of each year from 2012 to 2017. To avoid bias in investigating temporal trends of NDDs, we tried to contain populations with more than three different birth years in each year of diagnosis. The proportion of diagnosed cases based on the population subgroup in each sub-condition was calculated. The age of diagnosis was computed in years, since our data uses the age of diagnosis only in years, not in months.The prevalence of NDD was calculated by dividing the number of children diagnosed with NDD by the number of children who participated in the study. In addition, total cases were stratified by the degree of prematurity , sex, and socioeconomic status (categorized by medium-to-highest and the lowest), and differences between each selected characteristic were evaluated. The age of diagnosis was found to be skewed, as assessed by the Anderson–Darling test, and was presented with interquartile ranges. A logistic regression model was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (C.I) to investigate significant factors for cases of NDD. The selected variables were the degree of prematurity, sex, and socioeconomic status. A univariable logistic regression analysis was performed to identify the association between the proportion of NDDs and preterm birth. A multivariable logistic regression analysis was performed after adjusting for sex and socioeconomic status. The probability of NDD based on age at the time of diagnosis were presented with Kaplan–Meier survival curves and compared among population subgroups using the log-rank test. Statistical analysis was performed using SAS version 9.4 .The baseline demographic characteristics of children with NDD are summarized in p < 0.001). The NDD-free probability of DD and CP in both preterm groups was higher than that of the FT group at the beginning of the observation period; however, during the latter phase, the NDD-free probability of ADHD, LD, and ID in both preterm groups increased rapidly and was ultimately higher than that of the FT group.The Kaplan–Meier survival curves for subgroups based on the age of diagnosis are presented in This nationwide population-based study investigated the impact of preterm birth on NDD in South Korea. Our study revealed that preterm birth is an evident risk factor for NDD; the odds of an overall diagnosis were 16.15 times higher in the EP/ELBW group and 4.46 times higher in the OP/LBW group. In addition, the preterm population accounted for a considerable proportion of diagnosed cases. Lastly, preterm birth had the most significant impact on ASD and DD, following CP.To the best of our knowledge, this is the first study in Asian countries to address the association between preterm birth and a wide spectrum of NDD using nationwide birth cohort data. Although there is likely an inflated preterm population who were monitored more closely with earlier diagnosis of NDD than children born with FT, our findings provide a valuable understanding of the national epidemiology of preterm infants with NDD in South Korea. Nevertheless, our study has several limitations which are associated with the characteristics of the raw data. First, as we selected study populations who assigned the birth codes of ICD-10, selection bias can occur. It is not obligatory for clinicians to assign birth codes regarding both GA and birth weight. To obtain as many individuals as possible, we entered subjects who assigned either one of the information. Second, we limited the age of interest to 0–6 years. Newly diagnosed cases or individuals diagnosed with one or more morbidities later than six years of age could not be calculated. Additionally, the observed time period among individuals varied from three to six years. Therefore, a gap between our findings and actual incidences might exist. Third, we could not consider clinical  and environmental information  which are not registered in the form of ICD-10 codes. Additionally, our study design may have overlooked co-morbidity cases and sub-clinical neurodevelopmental problems. Lastly, we could not consider individuals with undernutrition, and growth restrictions.Risk factors associated with NDD are not yet completely understood and are expected to be multifactorial . RegardiPrevious studies have shown that preterm birth is a significant risk factor for NDD. Recent meta-analysis studies have shown that the preterm population has as much as a three-fold increase in the aOR of NDD compared to the control group ,17,23. OCP, which marked the highest aOR among NDDs, is a widely known sequela of preterm birth. Based on a nationwide study in South Korea , DD, ASDIn addition, considering that DD has high comorbidity to ASD , it shouIn addition, the preterm population showed an increasing trend and significant impact on both ADHD and LD. This was in line with a previous Swedish nationwide study, which showed that the risk of ADHD was inversely related to GA . As showOur study examined the prevalence and trend of NDD and the impact of preterm birth using nationwide data. The risk of NDD was considerably increased by the degree of prematurity, and this tendency was more prominent in ASD and DD. We emphasize the importance of NDD as preterm birth-related morbidity, and further intervention and management programs should be implemented.


The USA has higher rates of preterm birth and incarceration than any other developed nation, with rates of both being highest in Southern states and among Black Americans, potentially due to rurality and socioeconomic factors. To test our hypothesis that prior-year county-level rates of jail admission, economic distress, and rurality were positively associated with premature birth rates in the county of delivery in 2019 and that the strength of these associations is greater for Black women than for White or Hispanic women, we merged five datasets to perform multivariable analysis of data from 766 counties across 12 Southern/rural states.We used multivariable linear regression to model the percentage of babies born premature, stratified by Black (Model 1), Hispanic (Model 2), and White (Model 3) mothers. Each model included all three independent variables of interest measured using data from the Vera Institute, Distressed Communities Index, and Index of Relative Rurality.F = 33.81, p < 0.0001) and White  mothers. Rurality was associated with premature births among White mothers . Jail admission rate was not associated with premature births among any racial group, and none of the study variables were associated with premature births among Hispanic mothers.In fully fitted stratified models, economic distress was positively associated with premature births among Black (Understanding the connections between preterm birth and enduring structural inequities is a necessary scientific endeavor to advance to later translational stages in health-disparities research The USA continues to have the highest preterm birth rate  of any high-income country . In 2021Due to the severity of this public health crisis, the March of Dimes convened a multi-disciplinary group to develop a consensus statement on the causes of the Black–White disparity in preterm birth in the USA. The group identified 33 hypothesized causes and concluded that structural racism was the only upstream factor that fully explained unique epidemiologic findings in the Black–White disparity in preterm birth, including the lack of disparity between African-born Black women and US-born White women and the lack of protection against preterm birth afforded by educational and economic gains made by US-born Black women . FortunaData from Southern and rural US states provide a unique shared context by which to study preterm birth and factors related to structural racism. Southern and rural states have some of the highest rates of preterm birth in the country  and haveAs for preterm birth outcomes for the USA and South, Black people in the nation and region are up to 5 times more likely than White people to be incarcerated ,15. IncaConsequently, both direct and indirect ICJS can have health and socioeconomic consequences that increase the risk of preterm births and magnify existing racial disparities ,23–25. TLiving in neighborhoods of concentrated poverty and disadvantage is a contributing factor across all racial and ethnic groups to both incarceration and preterm births ,34–36. IHowever, the relationship between socioeconomic factors and preterm birth is not as clear as it is between poverty and incarceration. For instance, the greatest disparity in Black–White preterm birth rates is found between US-born Black and White women of high socioeconomic status because Black women do not experience the same benefits of education and income as White women . AdditioOur county-level research contributes to this growing literature by examining preterm birth rates of women living within the nexus of poverty, mass incarceration, and rurality. Black Americans are more than twice as likely as White Americans to report having a family member or sexual partner who has been or is incarcerated, on probation, or on parole ,20,23,42Investigation of the relationship between preterm births and county-level incarceration is of the utmost importance, as it provides an in-depth and nuanced narrative of national trends in birth outcome and criminal justice disparities. However, the investigation of the relationship between incarceration, preterm birth, and poverty is still a nascent field of study, and gaps remain in the literature. The purpose of this study was to examine the influence of county-level incarceration and poverty indicators on racial disparities in preterm birth in US counties of delivery. Our study tests the hypothesis that county-level jail admission rates in 2018, county-level economic distress, and rurality will be positively associated with preterm birth rates in the county of the delivery in 2019 and that the strength of these associations will be greater for Black women than for White or Hispanic women.We drew on multiple county-level data sources to create a comprehensive profile of county characteristics across 766 counties in 12 Southern and/or rural states in the USA . All datasets were merged using a five-digit Federal Information Processing System (FIPS) county identifier code. We used data from the CDC National Environmental Public Health Tracking System (NEPHT) to calculate preterm birth rates, which we defined as the percentage of live singleton births born before 37 completed weeks of gestation to Black, Hispanic, or White women who gave birth in that county in 2019 . PregnanWe used jail admission data available through the Vera Institute . ImportaWe used the most recent Distressed Communities Index  to measure the overall level of economic stress for each county . The DCIFinally, we used the Index of Relative Rurality (IRR) to determine geographic differences between counties . The IRRp < 0.01; Hispanic, KS = 0.17, p < 0.01; White, KS = 0.19, p < 0.01), thus requiring no non-linear model specifications. We reported the F-value for the Type III fixed-effects solution for each independent variable to ease interpretation of results and comparability between variables and groups using a log-transformed outcome.All analyses were performed with SAS software (v9.4). We generated summary statistics for each study variable, including the mean and standard deviation. We used linear regression to model the bivariate associations between premature birth and each independent variable. Because three premature birth values were recorded for each county , we stratified our regression models by racial/ethnic group. We applied a log transformation to the Black, Hispanic, and White dependent variables of the percentage of births to achieve a normal distribution for use in linear models. Our transformed outcomes of the percentage of preterm births normally distributed , Hispanic (Model 2), and White (Model 3) mothers. Each model included all three independent variables of interest, including county-level jail admission rate in 2018, the DCI, and the IRR. Given the wide range of demographic, social, and economic county characteristics included in the composite DCI score, we did not adjust for additional county characteristics.To determine if county-level jail admission rates in 2018, county-level economic distress, and rurality were associated with preterm birth rates in the county of delivery in 2019, we merged all five datasets to give complete data for 766 out of 1296 counties (59%) across 12 Southern/rural states in our sample. Table p < 0.0001 for each group). Jail admission rate was only positively associated with premature births among White mothers . In the fully fitted stratified models  and White  mothers. Rurality was only associated with premature births among White women . Jail admission rate was not associated with premature births among any racial group, and none of the study variables were associated with premature births among Hispanic mothers.In bivariate analyses, economic distress and rurality were positively and significantly associated with preterm births among Black and White women  and our predictors (jail admissions and economic distress). To address this, we used a composite score of economic distress derived from multiple social and economic determinants of health, including education, employment, poverty, income, housing, jobs, and business. As a result, we eliminated the problem of highly correlated predictors and simultaneously incorporated contextual factors into the study design. Additionally, because risks and exposures vary widely between urban and rural areas, we adjusted our models to include a dynamic measure of rurality.Second, the use of birth certificate-derived data from the NEPHT database limited us to investigating preterm birth rates based on county of delivery and not the county of residence. Future studies should evaluate the community environments where pregnant women live, as those environments may differ from where the baby was actually delivered. This is particularly true for pregnant women living rural counties because they are more likely to give birth outside their home county due to a lack of healthcare services. We adjusted our model for rurality to help parse out this disparity, but it is still an important limitation. To our knowledge, there are no national or regional publicly available datasets that have individual-level information about birth outcomes and other individual characteristics. This is an important limitation of national and regional CDC surveillance data and has implications for how we interpret county-level findings.Like the NEPHT, the most recent Vera county-level jail admission data do not include individual-level data such as race, ethnicity, gender, and residence; it only includes aggregate information about the total number of jail admissions for a given county where individuals were incarcerated. While we acknowledge this is an important limitation, the USA has more than 3000 counties, most of which have their own jail facility, making it untenable to contact each of these jails to obtain demographic data. Despite its limitations, the Vera dataset is, to our knowledge, the only publicly available national incarceration dataset, which makes building collaborations with local community-based partners involved in the criminal justice system especially important to advance this field of research. Future research should apply the principles of community-based participatory research to build such collaborations .Despite the limitations, the scope of our county-level study provides an epidemiologic narrative of disparities that may inform the design of future multilevel studies. Strengths of the study were the use of a novel measure of economic well-being and our accounting for shared historical context by analyzing data from counties in Southern and rural states. Additionally, our inferences about the risk of preterm birth among women in the US South were based on analytic results from aggregate, county-level variables collected from these secondary databases. However, county-level measurement may mask nuanced differences between neighborhoods, requiring more granular assessment than even zip codes or census tracts offer . For insOur study identified differential associations between economic distress and preterm birth, with notable concentrations of high poverty and high preterm birth rates in the US South. Despite the USA far outpacing other countries in healthcare expenditures, Black women in some of the counties we studied had preterm birth rates that were higher than the rates found in many low-income countries . RegardlOur study contributes to literature aimed at informing policy-making and programmatic decisions regarding the deleterious health effects of the social and economic determinants of health associated with community distress. Our findings echo the importance of investing in the economic well-being of distressed communities to affect downstream health outcomes, including preterm birth. Future research should examine and test ways that community-level interventions can improve economic and structural environmental factors to influence preterm birth rates. Future research should also use mixed methodological approaches to conduct in-depth investigations of the influence of distressed community environments on pregnancy experiences and diverse exposures to the criminal justice system across the life course of Black and White women in the South. Given mixed findings in the extant literature, both qualitative and quantitative data are needed to elucidate the true relationship between incarceration and preterm birth at key stages of a woman’s reproductive life cycle. Future research should be informed by interdisciplinary theoretical frameworks that will inform the conceptualization and measurement of indicators of structural racism. Lastly, future studies should continue to examine, at appropriate population levels, the relationship between preterm birth and socioenvironmental factors, including those accounted for in the DCI. Although not perfect, the identification of specific factors driving this strong association can inform the development and testing of translational health-disparities interventions in the future.


Birth is a physiological act that is part of the morpho-functional economy of the maternal body. Each stage in the act of birth has a predetermined pathway that is neurohormonally induced and morpho-functionally established through specific and characteristic adaptations. Like maternity, childbirth also has an important impact on the maternal body as a biological structure and psycho-emotional behavior. Cesarean section performed at the request of the mother with no medical underlying conditions besides the prolonged hospitalization risk can also cause breathing problems in children, delayed breastfeeding, and possible complications in a future pregnancy. Vaginal birth remains the path of choice for a physiological evolution pregnancy. Although erroneously considered safe and easy today, cesarean section delivery must remain an emergency procedure or a procedure recommended for pregnancies where birth is a risk to the mother and to the child, as cesarean section itself is a risk factor for negative outcomes for both mother and baby. This review summarizes the impact that both cesarean section and natural birth have on mother and newborn in their attempt to adapt to postpartum events and extrauterine life. When we talk about vaginal birth or cesarean birth, we have in mind childbirth, that is, the process by which the product of conception—the newborn—separates from the maternal environment and begins its life under completely new conditions. Physiologically, this passage is gradual and phased, equally including maternal participation and fetal adaptation in an absolutely physiological manner that characterizes labor for the human species ,2. The WThe aim of this review is to summarize the impact that both cesarean section and natural birth have on mother and newborn regarding their physical and emotional health in their attempt to adapt to postpartum period and childcare for the mother and to extrauterine life for the newborn.To understand the adaptation effort to which the mother and newborn are subjected, a brief incursion into the physiology of birth with its two components is necessary. First, the maternal component prepares the act of childbirth through a series of morpho-functional changes facilitating the evolution of birth. Thus, labor, for example, is preceded by hormonal changes starting 3 to 4 weeks before the actual moment . Labor iNote that all these changes occur over time, and their actual performance in childbirth takes 8–12 h. Apart from the local pelvic-genital changes, there are changes and adaptation incurred by all organs, apparatuses, and systems of the maternal body. Thus, the rhythm and amplitude of breathing increases by about 20% (24–26 rpm and 600 mL of the current volume), heart rhythm increases to 80–85/min, AP increases by 10–20 mmHg, and cardiac output by 20–30% ,16; withIn labor context, maternal suffering is notable and is characterized by pain (labor pain) generated by uterine contractions, compression, and traction on the pelvic-genital structures . Labor p A separate remark must be made as regards the psychic component through the emotional state, depression, and stress it implies, which may interfere negatively with the evolution of pregnancy. It is estimated that the global prevalence of postpartum depression (PPD) is approximately 17%, directly associated with country development and national or regional income ,24. The The major impact of the act of childbirth on the baby is the absolute need for immediate and subsequently gradual adaptation to a new environment of life: the extrauterine medium where the conditions are completely different and require a considerable effort of adaptation from the newborn. However, it is a complex physiological process that is verified in time and that, under normal circumstances, is concluded with the emergence of the parent–child couple ,9. BeyonThe exact nature of fetal pain remains unknown, but there is evidence that the fetus experiences pain in the third trimester of pregnancy . The perSimply, the newborn can express pain only at the moment of his first breath, which is nothing more than a scream of pain followed by crying that most of those present consider an expression of life and vitality when it actually comes from an underlying pain accumulated throughout birth. Crucial changes, however, are the functional changes that occur with birth because the morphological changes are reduced to skull changes, as it becomes ovoid by overlapping the sutures due to the compression of the pelvic-genital passage with the risk of hemorrhage  . The preHowever, a certain degree of perinatal stress is beneficial during childbirth, as it increases the synthesis of cortisol and catecholamine in the infant’s blood; these are hormones of great importance for the achievement of pulmonary maturity and for the adaptation of the circulatory system to extrauterine life ,45.Of vital importance, however, are the functional changes of the vital organs of the lung and heart that provide the vital functions: breathing and circulation, which occurs spontaneously with the sudden passage to the extrauterine life. According to Schuler et al.’s study, newborns delivered through the birth canal achieve higher cortisol levels and present an increased expression of pain compared to neonates delivered by cesarean section .The lungs are still full of liquid until the first breath. The first inspiratory effort plays a critical role by generating an active pressure gradient that allows the fluid to pass into the interstitial tissue, from where it will be gradually removed by pulmonary and lymphatic circulation . The firAll these will be followed by specific care, natural nutrition , and the psycho-affective and environmental stimulation of the mother–child couple, which will be the expression of the normal physiological evolution of vaginal birth. We emphasize that the above mentioned can be circumscribed to 95% of births .Every obstetrics textbook has a chapter entitled pathology of labor, which, of course, refers to situations where, for various reasons, birth does not progress, progresses slowly, or stops evolving.Many situations that affect birth belong to the pathology of pregnancy, which can be equally maternal, i.e., consuming diseases, basin dystocia, or congenital malformations; related to pregnancy, i.e., twins or malformations; or they may be related to the fetus, i.e., position dystocia, congenital malformations, hydrocephalus, or other situations that make it impossible or risky to give birth through the birth canal . Today, In India and Egypt, it was practiced since the year 600 BC, and the legal regulations were instituted in the time of the Roman King Numa Pompilius in the Lex Regia, which specifically provided cesarean as a mean of extracting the child from his deceased mother. This provision could also be found in Lex Caesarea during the time of Emperor Julius Caesar somewhere between 46–44 BC, hence the name Cesarean section ,52.The first mention in a medical book dates back to 1350, and the first measures to apply for the parturient in difficulty belonged to Ambroise Paré in 1550 and Jeremias Trautmann in 1610, whose patient died 25 days after through septicemia. Hemorrhage, peritonitis, and septicemia were major hazards until 1882 when Sänger introduced the surgical wound suture , in 1876 when Foster introduced asepsis and antisepsis, in 1847 when Simson introduced anesthesia, and in 1907 when Frank of Bonn and Hugo Selheim performed the incision on the lower uterine segment, bypassing the contractile area of the uterus and implicitly the peritoneal layer ,53. ModeIn many developed countries, the number of cesareans has increased, and attention has been focused on strategies to reduce its use, as it does not provide additional health gain but may increase maternal risks, and it may have implications for future pregnancies and health services ,58,59,60Another common reason for cesarean section is the phenomenon of defensive medicine. Defensive medicine seems to be related to gynecologists’ fear of legal actions promoted by their patients for medical malpractice and negligence .Additional concerns and controversies related to cesarean section include inequalities in the use of the procedure not only between countries but also within countries as well as the costs they impose on health systems ,64. For A contributor to the increased cesarean section levels might be the remuneration system that pays the same amount for vaginal and cesarean birth regardless of the prolonged assistance hours given in vaginal deliveries .The highest cesarean section rates are found in Latin America and the Caribbean (40.5%), and the lowest rates are found in sub-Saharan Africa , indicatIt is true that modern technical possibilities also highlight many situations that could negatively influence the evolution of pregnancies that would require a cesarean section as a necessity .Cesarean surgery is actually a brutal interruption of cohabitation of the fetus with his mother through the surgical separation that this procedure implies. It can be said that although the intervention is scheduled, and the psychological preparation of the mother is fulfilled, physiologically, neither the maternal nor the fetus’s body is prepared . It meanWHO’s recommendation of initiating breastfeeding is within one hour of birth . AlthougAs for the number of cesarean sections a woman can have, research has not established an exact number of repeat cesarean sections considered safe. Compared with primary caesarian section, multiple repeat caesarean sections (MRCS) are associated with additional risks including placenta previa, abnormal placental invasion, and difficulties in surgical dissection ,82. FurtThis impact is not less important because the same intervals that physiological birth implies are bypassed through cesarean. The slow adaptation to the new living environment involved by the passage through the pelvic-genital canal is brutally interrupted. The first breath is no longer the result of decompression of the thorax that passed through the pelvic strain but the result of artificial skin stimulation, thoracic massage, or ventilation with the balloon. The presence of the anesthetic in the fetal circulation diminishes the tone and reflexes of the newborn, delaying the immediate adaptation reaction.It is known that the newborn needs >5 min to attain an arterial oxygen saturation >80% and almost 10 min to reach 90% during a normal postnatal transition . CesareaKnigin et al. evaluated the effect of maternal hypotension after spinal anesthesia for elective cesarean and the time from anesthesia to delivery as risk factors for neonatal acidosis. Anesthesia-to-incision and incision-to-delivery intervals, use of vasopressor treatment, and sustained spinal hypotension were independently associated with neonatal acidosis. However, no neonatal complications such as transient tachypnea of the newborn, respiratory distress, or admission to NICU were encountered. Other factors such as maternal age, the number of previous cesarean deliveries, gestational age, neonatal birthweight, and fetal presentation were not associated with neonatal acidosis . In terms of newborn cerebral oxygen saturation measured immediately after cesarean delivery, Willfurth et al. concluded that cerebral tissue oxygenation in neonates during immediate transition after birth was similar after maternal general and spinal anesthesia despite differences in SpO2, heart rate (HR), and APGAR score in term neonates. In preterm neonates, there were no statistically significant differences in SpO2, HR, and cerebral oxygen saturation between the two groups of study. Only the APGAR score in the 1st minute was significant lower in the general anesthesia group . In contThe absence of positive stimuli determined by the mother–child relationship that is delayed in cesarean delivery would negatively influence the child’s adaptation, especially because nutrition is delayed by the absence of lactation or the impossibility to practice it during the first 24 h ,2,8. TheRegarding the pediatric consequences of cesarean section, several studies concluded that cesarean section is a risk factor for respiratory tract infections, asthma, obesity, and neurological disorders in children . CurrentDuring the last years, the relationship between cesarean section and childhood asthma has been a subject of debate, with contradictory opinions available in the literature. Darabi et al., in their systematic review and meta-analysis, concluded that cesarean section, whether elective or performed for emergency reasons, increased the risk of childhood asthma . The lacLavin et al. compared the risk of obesity in childhood of children born through cesarean section (elective and performed in emergency) and children born through vaginal birth. Their findings suggested that there might be an association between cesarean section and childhood overweight . ConcernCesarean section is thought to have a negative effect on early brain development. Zhang et al. conducted a systematic review and meta-analysis to evaluate neurodevelopment and psychiatric pathologies in children delivered via cesarean section compared to those born through vaginal birth. They concluded that cesarean section was associated with an increased risk of several disorders. Autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) were most statistically significant . SimilarBirth is a physiological act that is part of the morpho-functional economy of the maternal body. Each stage in the act of birth has a predetermined pathway that is neurohormonally induced and morpho-functionally established through specific and characteristic adaptations. Like maternity, childbirth also has an important impact on the maternal body as a biological structure and psycho-emotional behavior as well as on her social life and relationships.The passage through the pelvic-genital canal in the act of childbirth is accompanied by important functional processes with a decisive role in adapting the newborn to extrauterine life, with beneficial effects on both the mother and child. Mother–child cohabitation and breastfeeding can be restored after the physiological birth.Vaginal birth remains the path of choice for a physiological evolution of pregnancy. Although erroneously considered safe and easy today, cesarean section delivery must remain an emergency procedure or a procedure recommended for pregnancies where birth is a risk to the mother and to the child.


Extra energy intake is commonly recommended for pregnant women to support fetal growth. However, relevant data regarding variations in energy intake and expenditure, body mass index and gestational weight gain (GWG) are frequently not considered. This study aimed to investigate how energy intake during pregnancy and gestational weight gain (GWG) are associated with birth weight.Early pregnant women were recruited into a Japanese nationwide prospective birth cohort study between 2011 and 2014. We analysed data of 89,817 mother-child pairs of live-born non-anomalous singletons after excluding births before 28 weeks or after 42 weeks. Energy intake during pregnancy was estimated from self-administered food frequency questionnaires (FFQ) and was stratified into low, medium, and high. Participants completed the FFQ in mid-pregnancy (mean 27.9 weeks) by recalling food consumption at the beginning of pregnancy. Effects of energy intake on birth weight and mediation by GWG were estimated using the Karlson–Holm–Breen method; the method separates the impact of confounding in the comparison of conditional and unconditional parameter estimates in nonlinear probability models. Relative risks and risk differences for abnormal birth size were calculated.Mean daily energy intake, GWG, and birth weight were 1682.1 (533.6) kcal, 10.3 (4.0) kg, and 3032.3 (401.4) g, respectively. 6767 and 9010 women had small-for-gestational-age and large-for-gestational-age infants, respectively. Relative to low energy intake, moderate and high intakes increased adjusted birth weights by 13 g and 24 g, respectively: 58 and 69% of these effects, respectively, were mediated by GWG. Compared with the moderate energy intake group, the low energy intake group had seven more women per 1000 women with a small-for-gestational-age birth, whereas the high energy intake group had eight more women per 1000 women with a large-for-gestational-age birth.GWG mediates the effect of energy intake on birth weight. All pregnant women should be given adequate nutritional guidance for optimal GWG and fetal growth. Fetal growth and birth weight are determined by a complex interaction among several maternal, pregnancy-related, and fetal-related factors. Extreme pre-pregnancy body mass indexes (BMIs), insufficient or excessive gestational weight gain (GWG), imbalanced nutrition, alcohol consumption and smoking, maternal diabetes and hypertension, multiple pregnancies, and preterm birth have all been associated with abnormal size of newborns –5.Appropriate GWG has been investigated based on pre-pregnancy BMI, and several organisations have proposed GWG guidelines , 7 for pTherefore, the present study aimed to investigate how energy intake during pregnancy and GWG are associated with birth weight and distinguish between the direct association of energy intake and indirect association mediated by GWG. Furthermore, we aimed to evaluate how different levels of energy intake affect birth size  in a cohort of singleton pregnancies from the Japan Environment and Children’s Study (JECS) .The JECS aims to explore environmental factors that affect the health and development of children and is being by the Environment, Japan. The detailed methodology and baseline profile of the study participants have been reported previously , 17. BriThis study uses the jecs-ag-20,160,424 dataset (released in June 2016) from the JECS, which comprises information from 104,102 fetal records. Therefore, formal sample size calculation was not performed in the present study. We restricted this study to 97,182 pregnancies resulting in live singleton births with no major birth defects. Then, we excluded participants based on predetermined exclusion criteria related to our exposure and outcome variables  , 21. TheAnthropometric measurements of newborns, including birth weight (in grams) and gestational age at birth (in weeks), were extracted from medical records transcripts. Gestational age was calculated from the first day of the last menstrual period or by using ultrasound examinations of the fetus during the first trimester. Birth size was defined as small-for-gestational-age (SGA), appropriate-for-gestational-age (AGA), and large-for-gestational-age (LGA) for birth weights below the 10th percentile, 10th to 90th percentile, or above the 90th percentile, respectively, according to the Japanese parity and sex-specific neonatal birth weight chart for gestational age at birth .Demographic, medical condition, and pregnancy-related data were collected through self-administered standard questionnaires or from medical records. GWG (mediator variable) was calculated by subtracting the self-reported pre-pregnancy body weight from the last measured weight closest to childbirth. Pre-pregnancy BMI was calculated by dividing the self-reported pre-pregnancy body weight (in kilograms) by the square of the height (in metres). The following information was also obtained: socioeconomic and lifestyle information, such as education, alcohol consumption, and smoking; occupation during pregnancy; physical activity levels  ; medical2), ‘normal weight’ (18.5–24.9 kg/m2), and ‘overweight and obese’ (≥25 kg/m2). Because the Japanese physique is small and underweight by global standards, the Ministry of Health, Labour and Welfare (MHLW) has provided a guideline for pregnancy weight gain, calculated from the Japanese average and by pre-pregnancy BMI category. The participants were grouped into ‘low’, ‘appropriate’, and ‘high’ GWG categories (for descriptive statistics) within each pre-pregnancy BMI stratum. GWG was stratified by applying the appropriate GWG ranges of 9–12 kg and 7–12 kg for underweight and normal-weight pregnant women, respectively, according to the recommendations of the Ministry of Health, Labour, and Welfare, Japan [2) and obese (≥30 kg/m2) pregnant women, respectively. The participants were categorised into three age groups: ≤25, 26–35, and ≥ 36 years. Maternal educational attainment was stratified into three groups: ‘high school or less’, ‘vocational school/college’, and ‘university or higher education’. Considering that activity level may vary across job types [Daily energy intake during pregnancy was stratified into three levels  comprising approximately equal numbers of participants. The tertiles were the 33.4 and 67.9 percentiles, corresponding to the energy intake values of 1412 kcal and 1856 kcal, respectively. GWG was analysed as a continuous variable. Birth weight was studied as a continuous variable and birth size in categories . Pre-pregnancy BMI was stratified as ‘underweight’ (< 18.5 kg/m obese’ ≥ kg/m2. B2), type of occupation and physical activity level during pregnancy, alcohol consumption and smoking during pregnancy, the presence of chronic diseases, receipt of health guidance, and nausea and vomiting during pregnancy. To increase the precision of the estimates, newborn sex and gestational age (weeks) were also adjusted. Next, we evaluated the associations between levels of energy intake (moderate energy intake as the referent) and birth size using a multinomial logistic regression model. The crude and adjusted relative risk ratios (RRR), adjusted risk differences, and corresponding 95% confidence intervals (CIs) for SGA and LGA births were reported. The same factors included in the mediation analysis, except newborn sex and gestational age, were included in the adjusted model. Additionally, we examined the characteristics of the women according to their inclusion status in our analysis. All statistical analyses were performed using Stata/MP version 15.1 . Statistical significance was defined as a two-sided P-value < 0.05.Descriptive statistics of the participants were calculated for the entire study population and according to the levels of energy intake. The mean and standard deviation for continuous variables and numbers and percentages for categorical variables are reported. Since our primary aim was to examine how energy intake during pregnancy and GWG are associated with birth weight, we performed a mediation analysis. Figure This study was conducted according to the principles expressed in the Declaration of Helsinki. All procedures involving human participants were approved by the Japan Ministry of the Environment’s Institutional Review Board on Epidemiological Studies (No. 100910001) and the Ethics Committees of all participating institutions. Written informed consent was obtained from all participants.Of the 97,182 eligible pregnancies reviewed, 7365 were excluded because they met the predetermined exclusion criteria. Thus, 89,817 (92.4%) mother-child pairs of live-born non-anomalous singletons remained for analyses  in our analysis.This study also has some limitations. For example, 16% of our cohort was underweight; thus, the findings of this study may not be generalisable to the entire obstetric population. Furthermore, our analysis relied solely on dietary information collected at a single time point during pregnancy. Dietary intake could have changed according to the stage of pregnancy. Considering the various dietary changes, including those caused by the occurrence of nausea and vomiting during pregnancy, evaluating the diet at only one point does not give is not a complete dietary assessment across the entire pregnancy. However, a previous study  reportedThere is a discrepancy between studies investigating the effects of maternal energy intake on fetal growth and birth weight. The reasons could be the heterogeneity in the study cohorts and analytical methods employed. We found a positive association between energy intake during pregnancy and birth weight in a Japanese cohort of non-anomalous singleton pregnancies, where GWG mediated a significant portion of the association. Because both extremes in energy intake during pregnancy increase the risk of abnormal birth size, we suggest that nutritional guidance be offered to all pregnant women to ensure appropriate nutrition for optimal GWG and fetal growth.


To assess how many adults remember their own birth weight, an important anamnestic item for cardiovascular and renal disease risk stratification, we conducted an inquiry among all employees of public hospitals of Ente Ospedaliero Cantonale (EOC) in Ticino region (Southern Switzerland). The results show that the vast majority of adults remember their own birth weight. Hence, it is reasonable to include this information in the stratification of risk for cardiovascular and renal diseases. Low birth weight confers an increased risk for cardiovascular and renal diseases . ConsequLike hypertension, physical inactivity, excessive body weight, smoking, diabetes, abnormal lipids and a positive family history of premature cardiovascular disease, low birth weight is a also relevant cardiovascular risk factor in adulthood , 3. NeveTo assess how many adults remember their own birth weight, all  employees of public hospitals of Ente Ospedaliero Cantonale (EOC) in Ticino region (Southern Switzerland) were invited to fill in a close-ended web-based questionnaire addressing, among others, own weight at birth. Since the analysis was completely anonymous, the institutional review board waived the necessity to have approval for this type of study. In an effort to get as much information as possible, we analyzed the responses to 12 questions: 6 questions about demographic data of the participants, 3 questions about knowledge of birth weight, birth length, and duration of pregnancy, 2 questions about cardiovascular risk factors and diseases and their pharmacotherapy, and one question to assess how the participants get the birth information.U-test was conducted to compare the two groups. All statistical analyses were performed using the GraphPad Prism® software version 8.0 . Significance was defined at p < 0.05.Low birth weight was defined as weight of less than 2,500 g. Continuous data are presented as median values with interquartile range or minimum and maximum range, and categorical data are presented as frequencies and percentages calculated from single answers. A comparison of prevalence between groups was performed by Fisher exact test. Mann-Whitney p < 0.01]. Median declared birth weight was 3,300 g . Low birth weight was present in 8.2% of the subjects, and 13% of the subjects presented at least one cardiovascular risk factor or disease. A trend toward an association between low birth weight and higher body mass index or cardiovascular diseases was found in this cohort (p = 0.16).A total of 1,369 (27%) employees answered the questionnaire, 1,054 (77%) were female and 315 (23%) were male. They ranged in the ages of 17 to 67 years (median 40 years), 677 (49%) were younger than 40 years, and 692 (51%) were 40 years of age or older. Twenty-one (1%) had an educational level of secondary school or less, 682 (54%) had higher professional education, and 567 (45%) had an university degree. but for 99 participants the educational level was not known. The profile of the employees who answered was similar to that of all employees . A total of 1164 (85%) declared to remember their own birth weight, the majority (70%) of them knew this fact by heart, 24% asked their parents, and 6% searched this information on birth documents at home. The knowledge of birth weight was slightly but significantly lower in the subjects 40 years of age or older [572 out of 692 (83%) vs. 593 out of 677 (88%); The majority of the adults remember their own birth weight, but the knowledge of it seems to be slightly lower in the elderly subjects. These conclusions might be flawed by some limitations. Given the rather low response rate (27%), our results should be considered preliminary and further confirmation is needed. Nevertheless, the educational level of the employees who answered is similar to that of all employees. Also, the high percentage of women who answered is in line to the high percentage of women working in public hospitals of Ente Ospedaliero Cantonale (EOC) in Ticino, Switzerland.A possible bias of the results is the fact that the survey was carried out among hospital workers, and many of them are health professionals who generally have more knowledge of health history than the general population and that it is impossible to know the veracity of the data given in the survey by the participants since the answers for birth weight knowledge could not be confirmed with data from healthcare records. However, the birth weight distribution and mean values are in line with the reference birth weight percentiles .Although further studies conducted on the general population are needed to confirm the preliminary results, we can assume that in developed countries such as Switzerland birth weight is correctly remembered, as a good agreement between birth record and self-reported birth weight is normally observed . Hence, The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Canton of Ticino.AC-M: study design, collection of data, analysis of data, and first draft of the manuscript. OG: study design, analysis of data, and final draft of the manuscript. MB: study design and final draft of the manuscript. GS: study design, collection of data, analysis of data, and final draft of the manuscript. All authors contributed to the article and approved the submitted version.


Simulated events include neonatal infections, morbidity associated with preterm birth and consequences of caesarean birth. Deterministic and probabilistic sensitivity analyses (PSAs) were performed.QALYs, costs and incremental cost‐effectiveness ratio (ICER).In this population, immediate birth dominates expectant management: it is more effective  and it is cheaper . In one‐way sensitivity analysis, results are robust to all but the odds ratio estimating the relative effect on incidence of infections. Threshold analysis shows that the odds of infection only need to be >1.5% with expectant management for the benefit of avoiding infections to outweigh the disadvantages of immediate birth. In PSA, immediate birth is the preferred option in >80% of simulations.Neonatal GBS infections are expensive to treat and may result in substantial adverse health consequences. Therefore, immediate birth, which is associated with a reduced risk of neonatal infection compared with expectant management, is expected to generate better health outcomes and decreased lifetime costs.For women with preterm prelabour rupture of membranes and group B streptococcus in vaginal or urine samples, immediate birth is associated with improved health in their babies and reduced costs, compared with expectant management. For women with preterm prelabour rupture of membranes and group B streptococcus in vaginal or urine samples, immediate birth is associated with improved health in their babies and reduced costs, compared with expectant management. Vertical transmission of GBS is the most common cause of early‐onset neonatal sepsis in the UK.+0–36+6 weeks of gestation and vaginal or urine GBS detection.The objective of our analysis was to compare the benefits, harms and costs of immediate birth versus expectant management in women with prolonged PPROM at 342We undertook this analysis as part of an update to the National Institute for Health and Care Excellence (NICE) national guidance on the diagnosis and management of neonatal infection.microsoft excel . The simulated population is women with PPROM at 34+0–36+6 weeks of gestation and vaginal or urine GBS detection. The model was a cost–utility analysis (CUA) comparing two approaches: immediate birth and expectant management. We measure outcomes in quality‐adjusted life years (QALYs) and costs in 2018/19 GBP (£). Our primary outcome is an incremental cost‐effectiveness ratio (ICER), expressed as cost per QALY gained. The model has a lifetime horizon, to reflect all important differences in costs and outcomes between the two approaches. Nevertheless, all relevant transitions in the model happen within 72 h of birth. The analysis adopts a UK National Health Service (NHS) and personal social services (PSS) perspective. Following standard UK practice, it discounts all costs and QALYs, applying a weight that is 3.5% lower for every year into the future that the outcomes occur.We built a decision model in The model comprises three independent decision trees Figure . The fir2.1Table 2.1.1The estimates we use to capture the effects of the strategies come from systematic reviews of relevant randomised controlled trials (RCTs).2.1.2The model estimates QALYs for both mothers and babies using UK‐based EQ‐5D data sources. For the mother, we apply utility decrements in the event of subsequent miscarriage or ectopic pregnancy. In the event of stillbirth, we apply a decrement reflecting the QALYs the baby would have accumulated over an average lifetime had they survived, equivalent to 25.06 discounted QALYs. We also apply a QALY decrement dependent on the duration of neonatal critical care to account for the extreme stress that parents experience ; see 2.1.3We estimate antenatal care costs using reported resource use from the economic evaluation accompanying the PPROMT RCT and multiplying those by costs reported from NHS reference costs for 2016/2017 and subsequently inflating them to 2018/2019 prices.To estimate the costs for lifelong neurodevelopmental delay, we rely on publications from the EPICure longitudinal study of premature babies in the UK and Ireland.Finally, we use a weighted average of costs across different levels of control and frequency of exacerbations to estimate an annual cost for additional cases of asthma.2.2To address parameter uncertainty in our base case, we performed one‐way and probabilistic sensitivity analyses. In one‐way sensitivity analysis, we vary each model input in turn within the range of its uncertainty . In probabilistic sensitivity analysis, we assign distributions to each of the model inputs. The model draws estimates for each input simultaneously from their respective distributions and stores the results. We repeat this process for a set number of iterations . We plot the incremental costs and QALYs from each of these iterations on a cost–utility plane, indicating a ‘cloud’ of possible outcomes, given parameter uncertainty. We also present a cost‐effectiveness acceptability curve, showing the probability that each approach is optimal as we vary the value that we ascribe to 1 QALY.33.1Figure Bringing these together, we estimate that immediate birth results in average costs of £14,372 and average QALYs of 24.705, over the baby’s lifetime, whereas expectant management costs £19,311 and generates 24.371 QALYs, on average. As such, immediate birth is the dominant option, resulting in reduced costs and more QALYs .In one‐way sensitivity analysis see  S5 thereProbabilistic sensitivity analysis Figure  shows su44.1+0–36+6 weeks of gestation, immediate birth dominates expectant management: it is both cheaper and provides more QALYs. These results arise because our model predicts that the lifetime discounted costs and consequences associated with neonatal GBS infection far outweigh those that can be expected from the complications of late‐preterm birth. Our calculations quantify the potentially ruinous consequences of neonatal GBS infection to babies, families, and the health and care system: the model estimates that an average infection is associated with discounted lifetime costs of approximately £40,000 and discounted lifetime effects of about 3.8 QALYs lost . This is why, even though the expected rates of infection are relatively low with either approach, immediate delivery is still associated with a substantial incremental QALY gain of 0.333 and cost savings of £4939, compared with expectant management for each case of PPROM. Sensitivity analysis shows that the OR estimating the relative likelihood of infection between the two approaches is the only meaningful contributor to decision uncertainty. At a 95% confidence level, the RCT data do not exclude either approach having a higher rate of infections; if there really were fewer infections with expectant management, it would become the preferred option.This economic analysis from a UK NHS and PSS perspective shows that, for women who test positive for GBS with PPROM at 344.2This is the first economic analysis of this decision problem (focusing on women with PPROM who test positive for GBS) and the first of any type of late‐preterm PPROM to estimate QALYs, accounting for lifelong morbidity and mortality. Its development was informed by a multidisciplinary committee of clinical and patient experts who advised on structure, assumptions and potential data sources, and provided validation of the model outputs.+0–36+6 weeks of gestation found a bronchopulmonary dysplasia incidence rate of 0.6% in its control arm;An ideal model of this problem would use evidence directly reporting lifelong effects of the two approaches. However, no such data exist. Our challenge was to move from the short‐term outcomes reported in RCTs to costs and QALYs over a lifetime. Estimating the impact of neonatal infections using observational evidence describing the mortality and morbidity with which events are associated is an established approach.Compared with many analyses of its type, our decision model has relatively few inputs that rely on expert consensus. However, we were unable to locate suitable estimates for the quality‐of‐life impacts of miscarriage, ectopic pregnancy and stillbirth in future pregnancies. To ensure our results are robust to the assumptions that we adopted, we tested the sensitivity of our model to extreme values and found that these have a negligible impact on the outputs see  S5. NeveThis analysis takes a UK NHS perspective, and the balance of benefits, harms and costs may vary among countries. Nevertheless, our sensitivity analyses suggest that in any setting in which immediate birth can be assumed to prevent infections it is likely to represent an effective use of resources, compared with expectant management. We have shown  S5 that 4.3We suggest that, regardless of any statistical uncertainty about which approach results in fewer infections, it is hard to specify plausible mechanisms by which immediate birth might increase the risk of infection to a greater degree than expectant management. If a woman with ruptured membranes is colonised with GBS the fetus remains in an environment in which both the potential pathogen and a portal for transmission are present, but this is less likely with immediate birth. It follows that infections must, to some degree, be more common with expectant management compared with immediate birth. Although we are uncertain about the magnitude of this effect, the model shows that the odds of GBS infection only need be 1.5% higher with expectant management for immediate birth to be the preferred approach.The NICE methods dictate that decision makers should consider QALYs as ‘of equal value regardless of other characteristics of the individuals, such as … age’.all pregnant women for GBS colonisation is not currently recommended in the UK,+0–36+6 weeks of gestation constitutes a ‘material fact’ in a post‐Montgomery era. If so, testing and an opportunity to undertake it with a full discussion of the implications of a positive or negative result should be a decision for the woman rather than the clinician.Our analysis only addresses a population in which the maternal GBS status is known. Although the routine antenatal screening of 5+0–36+6 weeks of gestation, the lifetime costs and harms of neonatal infection far outweigh those of preterm birth. Therefore, for women with PPROM who test positive for GBS, immediate birth, which minimises the risk of neonatal infection, generates better expected health outcomes and lower costs than expectant management.Our analysis suggests that, for babies at 34https://www.journalslibrary.nihr.ac.uk/programmes/hta/178606/#/) and iGBS3 . AS is a member of both the RCOG scientific advisory committee and the Royal College of Paediatrics and Child Health (RCPCH) quality improvement committee, and is the clinical lead at both the Kent and Medway Local Maternity system and the NHS South East Coast Neonatal Network. Completed disclosure of interests form available to view online as supporting information.JD, PB and GR have no conflicts of interest to declare. FC works at Novartis. The views expressed in this study are those of FC and not necessarily those of Novartis. SC‐D works at BresMed. The views expressed in this study are those of SC‐D and not necessarily those of BresMed. JP is the Chief Executive employed by Group B Strep Support, the Vice‐Chair of the RCOG Women’s Network and is a co‐applicant on GBS3 (GR, JP, PB and AS designed the analysis, with the help of the other NICE committee members acknowledged above. GR, FC, SC‐D and JD found parameters. GR and JD and analysed the data. JD, GR, JP, PB and AS provided the interpretation of results. JD wrote the first draft of the article. All authors critically revised the article and approved the final version for publication.As no human participants were involved in this theoretical analysis, no approval from an institutional review board was sought.Appendix S1Click here for additional data file.Data S1Click here for additional data file.Data S2Click here for additional data file.Data S3Click here for additional data file.Data S4Click here for additional data file.Data S5Click here for additional data file.Data S6Click here for additional data file.Data S7Click here for additional data file.


Objective: To assess the risk of necrotizing enterocolitis (NEC) and explore the relationship between antibiotic overexposure and disease occurrence in a large prospective birth cohort.Methods: Based on a prospective birth cohort, the study collected hospitalization data of very preterm infants (VPIs) having gestational age of less than 32 weeks from January 1, 2018, to June 30, 2021 via the China Northern Neonatal Network. Infants diagnosed with NEC ≥ stage II were included in the case group, and each case was matched for GA and birth weight for the control group. Furthermore, the risk factors for NEC were determined by statistical analyses.Results: A total of 6425 VPIs were included in this study, and 167 (2.6%) of these subjects were diagnosed with NEC ≥ stage II. The study also included 984 extremely preterm infants , including 50 (5.1%) infants diagnosed with NEC ≥ stage II. In the matched case-control study, subjects had a total of antibiotic days-of-therapy for 9015 days, of which broad-spectrum antibiotics (BSAs) accounted for 77%. The antibiotic spectrum index per antibiotic day in the case group was significantly higher and was an independent risk factor for the occurrence of NEC .Conclusion: The cohort of VPIs was overexposed to antiboitics. Unreasonable combination of antibiotics and overexposure to BSAs may increase the risk of NEC in preterm infants. Necrotizing enterocolitis (NEC) is a severe form of gastrointestinal infection that affects preterm babies in the majority of cases, and very preterm infants (VPIs) are at the highest risk of developing NEC. The incidence rate of NEC is about 2–6% , while tThe healthy gut microbiome is central to neonatal mucosal immunity and proper gut development. Notably, the use of antibiotics in the early postnatal period overlaps with the critical window of neonatal gut microbial colonization. Undoubtedly, long-term application and/or antibiotic overdosing can significantly hinder the normal physiological process of gut microbiome development in neonates due to the antibiotic-mediated killing of beneficial bacteria like Bifidobacteria in the intestine . An unbaThe Chinese Adverse Prognosis of VPIs (CARE-Preterm) cohort study involves the multicenter prospective dynamic observational cohorts of preterm infants, with data from a Sino-northern Neonatal Network (SNN) of 46 participating NICUs across six provinces and autonomous regions of northern China having a population of 120 million. Moreover, a large research-based database was dedicated to collecting real-world data and optimizing clinical management. According to our previous published studies , NEC is considered the leading cause of death of extremely preterm infants (GA ＜28 weeks) in the middle and late stages of hospitalization. The majority of preterm infants in this cohort reported having excessively prolonged antibiotic use, even with the combination of third-generation  and broad spectrum  in some instances . TherefoThis study was a multicenter, prospective, dynamically observed case-control study of the CARE-Preterm cohort of VPIs in China. The live births having GA of <32 weeks who were admitted to the participating units from January 1, 2018, to June 30, 2021 were selected for this investigation. Required data were retrieved from the SNN database.The study inclusion criteria were as follows: 1) GA at birth should be <32 weeks; and 2) the preterm neonate was admitted to the hospital within 24 h of live birth. The exclusion criteria included: 1) diagnosis with congenital gastrointestinal tract malformation; 2) congenital or inherited metabolic disorders; and 3) incomplete patient data.Children diagnosed with NEC ≥ stage II by Bell staging during the hospitalization were included in the case group, and each child was matched with 3 non-NEC infants according to their GAs (±3 days) and birth weights (±100 g), which constituted the control group.Length-of-therapy (LOT) was defined as the number of days a patient received antibiotics, irrespective of the variety of antibiotics. Days-of-therapy (DOT) was defined as the accumulated number of days of systemic antibiotic therapy . Both LOSmall for gestational age (SGA) was defined as a birth weight of less than 10th percentile for gestational age. Amniotic fluid pollution refers to the entry of meconium and other components into the amniotic fluid, causing the amniotic fluid to be turbid and abnormal in composition. Early onset sepsis (EOS) defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 h of birth. Bronchopulmonary dysplasia (BPD) was defined as oxygen requirement at 36 weeks of post-menstrual age . HemodynThe clinical data of each subject during hospitalization was collected that included- 1) patient demographics such as birth weight, GA, gender, SGA, multiple birth, postnatal Apgar score, admission temperature; 2) perinatal factors like prenatal hormone application, maternal hypertensive disorders of pregnancy (HDP), amniotic fluid contamination, duration of premature rupture of membranes (PROM) ≥18h, antibiotics used within 24 h of delivery; 3) NICU treatment records including days of invasive and non-invasive mechanical ventilation (the modes mainly include NIPPV and CPAP), use of pulmonary surfactant, age for starting intestinal feed, type of dairy feeding, and antibiotic use strategy; and (4) Complications during hospitalization: respiratory distress syndrome (RDS), EOS, BPD, EUGR and PNAC.NICU administration data were collected to the day before the onset of NEC in the case group.The data of the control group were collected to the same postnatal days.p < 0.05 was considered a statistically significant difference.All data was statistically analyzed using SPSS 26.0 software. Non-normal measures were expressed as medians and quartiles, and comparisons between groups were made using the Wilcoxon test or Kruskal–Wallis test; count data sets were expressed as cases (%), and comparisons between groups were made using the chi-square test or Fisher’s exact probability method. Variables that were not used as matching factors were subjected to one-way analysis, and those with statistically significant results were included in the multi-factor logistic analysis. Conditional logistic regression analysis was performed on the matched data to analyze the risk factors for the occurrence of NEC, and A total of 6425 VPIs were included in this study, and 167 (2.6%) neonates were diagnosed with NEC ≥ stage II. In this cohort, 984 extremely preterm infants (EPIs) were included, of which 50 (5.1%) neonates were diagnosed with NEC ≥ stage II. The mean age of onset of NEC was 19±12 days after birth. The inclusion process is shown in p <0.001) before matching. Based on the GA and birth weight, the control group was formed with 501 non-NEC infants. The two groups were well matched for GA and birth weight. The admission temperature was significantly lower in the case group as compared to that of the control group (p = 0.04)  .p = 0.006), which measured the breadth of the antimicrobial spectrum. However, there were no significant differences in LOT, DOT, and AUR between the two groups (p = 0.03). Enteral feeding was initiated earlier in the control group (p = 0.006).An in-depth analysis of the antibiotic use between these two groups showed that the total LOT of the two groups was 7177 days, accounting for 59% of the total observation period, and the LOT per infant was 11±8 days. The total DOT of the included populations was 9015 days, and the DOT per infant was 14±11 days. The DOT of BSAs was 6920 days, accounting for 77% of the total DOT. The case group had higher ASI per antibiotic day (o groups . Additiop = 0.45). The number of total prescriptions in the case group was significantly higher than that in the control group (p = 0.04), as shown in In the analysis of the types of antibiotics used, the third-generation cephalosporin was the most frequently prescribed medication (36.5% vs. 30.1%), but there was no significant difference between the two groups  in Comorbidity and death of preterm infants were higher in the case group as compared to those of the control group. Moreover, the extrauterine growth restriction (EUGR), parenteral nutrition-associated cholestasis (PNAC), and death were significantly associated with the occurrence of NEC in the multifactorial logistic regression analysis  days. During an average observation period of 19 days, the rate of exposure to antibiotics was almost 60%. Antibiotic exposure was generally long, with no significant differences between the two groups. The DOT was 13  days for the case group and 11 days for the control group. The DOT was longer than the LOT in both groups, suggesting a common antibiotic combination strategy in this cohort. These results were consistent with the findings of the previous investigations  conducteASI is a novel antibacterial metric that measures the breadth of antibiotic exposure. This study is the first to introduce the ASI to observe the association of broad-spectrum antibiotics with the occurrence of NEC. Compared with preterm infants without NEC in the control group, the ASI per antibiotic day was higher in the case group and was independently related to the occurrence of the disease, indicating that children with NEC may have a higher exposure to broader bactericidal spectrum prior to the disease onset. On the one hand, patients treated with BSAs in the early postnatal period may have severe disease symptoms and a higher risk of NEC. After the pathogen invades the intestinal tract of VPIs, it produces endotoxins like bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) that cause direct damage to the intestinal tract. It also causes a cascade of inflammatory responses by producing a variety of cellular pro-inflammatory factors, resulting in persistent damage to the intestinal wall . HoweverOn the other hand, the overexposure to antibiotis reflected by the high ASI per antibiotic days could itself be a risk factor for an increased rate of disease occurrence. Intestinal dysbiosis is considered the key link in the pathogenesis of NEC. The expansion of the antimicrobial spectrum exacerbates the reduction in the biodiversity of the intestinal microbiota, while the ability of the intestinal barrier to prevent the invasion of exogenous and potentially pathogenic microorganisms is also potentially suppressed . SeveralNEC is a multifactorial disease. This study only matched gestational age and birth weight, which had a significant impact on disease occurrence. Since this study could not cover all other aspects of NEC pathogenesis in preterm infants, it inevitably included selection bias. However, the study was real-world study based on a prospective birth cohort with data from a clinical research database. The ASI was introduced to delineate the possible causal relationship between severe antibiotic overexposure and NEC onset in VPIs. At the same time, the clinical data have been collected from multiple centers across China, which can truly reflect differences in the use of antibiotics between the low-and middle-income countries.Our study describes exposure to the antimicrobial spectrum and duration of antibiotics before onset in preterm infants with NEC, and highlights the severity of antibiotic over-use. Unreasonable combination of antibiotics and overexposure to broad-spectrum antibiotics may increase the risk of NEC in preterm infants. Moreover, this study provides with the baseline data for improving the quality of antibiotic treatment, optimizing the clinical management of premature infants.